57 results on '"Jan-Åke Liljeqvist"'
Search Results
2. COVID-19 in Pregnancy and Early Childhood (COPE): study protocol for a prospective, multicentre biobank, survey and database cohort study
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Anders Elfvin, Åsa Leijonhufvud, Sophia Brismar Wendel, Thomas Abrahamsson, Anna Wessberg, Helena Fadl, Maria Jonsson, Verena Sengpiel, Anna-Karin Wikström, Ulrika Aden, Ola Andersson, Lina Bergman, Marie Blomberg, Anna Sandström, Ylva Carlsson, Johanna Berg, Jan-Åke Liljeqvist, Mehreen Zaigham, Karolina Linden, Malin Veje, Hanna Östling, Anna Hagman, Anna Sand, Anna-Carin Wihlbäck, Elin Naurin, Emma Von Wowern, Gilda Dumitrescu, Gustaf Biasoletto, Johan Berg, Kathrin Rothbarth, Kristina Pettersson, Linda Hjertberg, Linda Iorizzo, Magnus Lindh, Maria Lindqvist, Maria Revelj, Maria Svenvik, Marie Vikström Bolin, Marie-Charlotte Nilsson, Matilda Friman Mathiasson, Merit Kullinger, Mirjana Janes-Nakic, Ove Karlsson, Pihla Kuusela, Sandra Holmström, Sofie Graner, Susanne Woxenius, and Åsa Pontén
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Medicine - Published
- 2021
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3. Correction: Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders.
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Emelie Marklund, Susannah Leach, Hannes Axelsson, Kristina Nyström, Heléne Norder, Mats Bemark, Davide Angeletti, Anna Lundgren, Staffan Nilsson, Lars-Magnus Andersson, Aylin Yilmaz, Magnus Lindh, Jan-Åke Liljeqvist, and Magnus Gisslén
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Medicine ,Science - Abstract
[This corrects the article DOI: 10.1371/journal.pone.0241104.].
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- 2021
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4. Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders.
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Emelie Marklund, Susannah Leach, Hannes Axelsson, Kristina Nyström, Heléne Norder, Mats Bemark, Davide Angeletti, Anna Lundgren, Staffan Nilsson, Lars-Magnus Andersson, Aylin Yilmaz, Magnus Lindh, Jan-Åke Liljeqvist, and Magnus Gisslén
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Medicine ,Science - Abstract
BackgroundTo accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset.MethodsSARS-CoV-2-specific IgG antibody levels were quantified using two clinically validated and widely used commercial serological assays (Architect, Abbott Laboratories and iFlash 1800, YHLO), detecting antibodies against the spike and nucleocapsid proteins.ResultsForty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P = 0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset.ConclusionsPatients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys.
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- 2020
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5. Rad51 and Rad52 are involved in homologous recombination of replicating herpes simplex virus DNA.
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Ka-Wei Tang, Peter Norberg, Martin Holmudden, Per Elias, and Jan-Åke Liljeqvist
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Medicine ,Science - Abstract
Replication of herpes simplex virus 1 is coupled to recombination, but the molecular mechanisms underlying this process are poorly characterized. The role of Rad51 and Rad52 recombinases in viral recombination was examined in human fibroblast cells 1BR.3.N (wild type) and in GM16097 with replication defects caused by mutations in DNA ligase I. Intermolecular recombination between viruses, tsS and tsK, harboring genetic markers gave rise to ∼17% recombinants in both cell lines. Knock-down of Rad51 and Rad52 by siRNA reduced production of recombinants to 11% and 5%, respectively, in wild type cells and to 3% and 5%, respectively, in GM16097 cells. The results indicate a specific role for Rad51 and Rad52 in recombination of replicating herpes simplex virus 1 DNA. Mixed infections using clinical isolates with restriction enzyme polymorphisms in the US4 and US7 genes revealed recombination frequencies of 0.7%/kbp in wild type cells and 4%/kbp in GM16097 cells. Finally, tandem repeats in the US7 gene remained stable upon serial passage, indicating a high fidelity of recombination in infected cells.
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- 2014
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6. A genome-wide comparative evolutionary analysis of herpes simplex virus type 1 and varicella zoster virus.
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Peter Norberg, Shaun Tyler, Alberto Severini, Rich Whitley, Jan-Åke Liljeqvist, and Tomas Bergström
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Medicine ,Science - Abstract
Herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) are closely related viruses causing lifelong infections. They are typically associated with mucocutaneous or skin lesions, but may also cause severe neurological or ophthalmic diseases, possibly due to viral- and/or host-genetic factors. Although these viruses are well characterized, genome-wide evolutionary studies have hitherto only been presented for VZV. Here, we present a genome-wide study on HSV-1. We also compared the evolutionary characteristics of HSV-1 with those for VZV. We demonstrate that, in contrast to VZV for which only a few ancient recombination events have been suggested, all HSV-1 genomes contain mosaic patterns of segments with different evolutionary origins. Thus, recombination seems to occur extremely frequent for HSV-1. We conclude by proposing a timescale for HSV-1 evolution, and by discussing putative underlying mechanisms for why these otherwise biologically similar viruses have such striking evolutionary differences.
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- 2011
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7. Longevity of anti-spike and anti-nucleocapsid antibodies after COVID-19 in solid organ transplant recipients compared to immunocompetent controls
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Emily de Coursey, Jesper Magnusson, Susannah Leach, Seema Baid-Agrawal, Carin Wallquist, Andreas Schult, Kristjan Karason, Lars-Magnus Andersson, Inger Holm Gunnarsson, Jan-Åke Liljeqvist, John Mackay Søfteland, Jan Stenström, Hanna Jacobsson, Magnus Gisslén, Mats Bemark, Marie Felldin, Jan Ekelund, Vanda Friman, and Anders Bergdahl
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medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,media_common.quotation_subject ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,medicine.medical_treatment ,Antibodies, Viral ,Gastroenterology ,Disease severity ,Internal medicine ,Humans ,Immunology and Allergy ,Medicine ,Pharmacology (medical) ,Longitudinal Studies ,media_common ,Transplantation ,biology ,SARS-CoV-2 ,business.industry ,Longevity ,COVID-19 ,Immunosuppression ,Organ Transplantation ,Transplant Recipients ,biology.protein ,Antibody ,business ,Solid organ transplantation ,Paired Analysis - Abstract
Solid organ transplant recipients (SOTRs) are on lifelong immunosuppression, which may interfere with adaptive immunity to COVID-19. The data on dynamics and duration of antibody response in SOTRs are limited. This longitudinal study examined the longevity of both anti-spike (S)- and anti-nucleocapsid (N)-specific IgG antibodies after COVID-19 in SOTRs compared to matched immunocompetent persons. SOTRs (n = 65) were matched with controls (n = 65) for COVID-19 disease severity, age, and sex in order of priority. Serum-IgG antibodies against N and S antigens of SARS-CoV-2 were analyzed. At 1 and 9 months after COVID-19, anti-S-IgG detectability decreased from 91% to 82% in SOTRs versus 100% to 95% in controls, whereas the anti-N-IgG decreased from 63% to 29% in SOTRs versus 89% to 46% in controls. A matched paired analysis showed SOTRs having significantly lower levels of anti-N-IgG at all time points (1 month p = .007, 3 months p .001, 6 months p = .019, and 9 months p = .021) but not anti-S-IgG at any time points. A mixed-model analysis confirmed these findings except for anti-S-IgG at 1 month (p = .005) and identified severity score as the most important predictor of antibody response. SOTRs mount comparable S-specific, but not N-specific, antibody responses to SARS-CoV-2 infection compared to immunocompetent controls.
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- 2022
8. COVID-19 in solid organ transplant recipients: A national cohort study from Sweden
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Emily de Coursey, Marie Felldin, John Mackay Søfteland, Susannah Leach, Jesper Magnusson, Gustav Friman, Bengt von Zur-Mühlen, Ali Reza Biglarnia, Hanna Jacobsson, Kristjan Karason, Ida Löfman, Vanda Friman, Andreas Schult, Bo-Göran Ericzon, Carin Wallquist, Per Lindnér, Mihai Oltean, Jan Ekelund, and Jan-Åke Liljeqvist
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Male ,immunosuppressant ,Patient characteristics ,Infektionsmedicin ,Cohort Studies ,infection and infectious agents ‐ viral ,Seroepidemiologic Studies ,clinical research / practice ,Immunology and Allergy ,organ transplantation in general ,Pharmacology (medical) ,patient characteristics ,dysfunction ,Middle Aged ,Early warning score ,practice ,infection and infectious agents ‐ ,Original Article ,medicine.symptom ,viral ,Infectious Medicine ,medicine.medical_specialty ,kidney (allograft) function ,Coronavirus disease 2019 (COVID-19) ,infectious disease ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Renal function ,Asymptomatic ,patient survival ,Internal medicine ,medicine ,Humans ,Seroprevalence ,Aged ,Retrospective Studies ,Sweden ,Transplantation ,kidney (allograft) function / dysfunction ,SARS-CoV-2 ,business.industry ,Kirurgi ,COVID-19 ,Original Articles ,Organ Transplantation ,health services and outcomes research ,Transplant Recipients ,clinical research ,Surgery ,Solid organ transplantation ,business - Abstract
Solid organ transplant (SOT) recipients run a high risk for adverse outcomes from COVID-19, with reported mortality around 19%. We retrospectively reviewed all known Swedish SOT recipients with RT-PCR confirmed COVID-19 between March 1 and November 20, 2020 and analyzed patient characteristics, management, and outcome. We identified 230 patients with a median age of 54.0 years (13.2), who were predominantly male (64%). Most patients were hospitalized (64%), but 36% remained outpatients. Age >50 and male sex were among predictors of transition from outpatient to inpatient status. National early warning Score 2 (NEWS2) at presentation was higher in non-survivors. Thirty-day all-cause mortality was 9.6% (15.0% for inpatients), increased with age and BMI, and was higher in men. Renal function decreased during COVID-19 but recovered in most patients. SARS-CoV-2 antibodies were identified in 78% of patients at 1-2 months post-infection. Nucleocapsid-specific antibodies decreased to 38% after 6-7 months, while spike-specific antibody responses were more durable. Seroprevalence in 559 asymptomatic patients was 1.4%. Many patients can be managed on an outpatient basis aided by risk stratification with age, sex, and NEWS2 score. Factors associated with adverse outcomes include older age, male sex, greater BMI, and a higher NEWS2 score.
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- 2021
9. Longitudinal Follow Up of Immune Responses to SARS-CoV-2 in Health Care Workers in Sweden With Several Different Commercial IgG-Assays, Measurement of Neutralizing Antibodies and CD4+ T-Cell Responses
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Emelie Marklund, Anna Lundgren, Jan-Åke Liljeqvist, Aylin Yilmaz, Susannah Leach, Staffan Nilsson, Lars-Magnus Andersson, Magnus Gisslén, Mats Bemark, and Kristina Nyström
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Adult ,CD4-Positive T-Lymphocytes ,Male ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Health Personnel ,Immunology ,Antibodies, Viral ,health care workers ,Serology ,Young Adult ,Immune system ,Seroepidemiologic Studies ,Pandemic ,Health care ,Immunology and Allergy ,Medicine ,Seroprevalence ,antibodies ,Humans ,neutralizing antibodies ,Pandemics ,Original Research ,Aged ,Sweden ,biology ,business.industry ,SARS-CoV-2 ,Immunity ,COVID-19 ,RC581-607 ,Middle Aged ,Antibodies, Neutralizing ,CD4+ T cells ,Immunoglobulin G ,biology.protein ,Female ,Antibody ,Immunologic diseases. Allergy ,business ,Follow-Up Studies - Abstract
BackgroundThe risk of SARS-CoV-2 infection among health care workers (HCWs) is a concern, but studies that conclusively determine whether HCWs are over-represented remain limited. Furthermore, methods used to confirm past infection vary and the immunological response after mild COVID-19 is still not well defined.Method314 HCWs were recruited from a Swedish Infectious Diseases clinic caring for COVID-19 patients. IgG antibodies were measured using two commercial assays (Abbot Architect nucleocapsid (N)-assay and YHLO iFlash-1800 N and spike (S)-assays) at five time-points, from March 2020 to January 2021, covering two pandemic waves. Seroprevalence was assessed in matched blood donors at three time-points. More extensive analyses were performed in 190 HCWs in September/October 2020, including two additional IgG-assays (DiaSorin LiaisonXL S1/S2 and Abbot Architect receptor-binding domain (RBD)-assays), neutralizing antibodies (NAbs), and CD4+ T-cell reactivity using an in-house developed in vitro whole-blood assay based on flow cytometric detection of activated cells after stimulation with Spike S1-subunit or Spike, Membrane and Nucleocapsid (SMN) overlapping peptide pools.FindingsSeroprevalence was higher among HCWs compared to sex and age-matched blood donors at all time-points. Seropositivity increased from 6.4% to 16.3% among HCWs between May 2020 and January 2021, compared to 3.6% to 11.9% among blood donors. We found significant correlations and high levels of agreement between NAbs and all four commercial IgG-assays. At 200-300 days post PCR-verified infection, there was a wide variation in sensitivity between the commercial IgG-assays, ranging from 90% in the RBD-assay. There was only moderate agreement between NAbs and CD4+ T-cell reactivity to S1 or SMN. Pre-existing CD4+ T-cell reactivity was present in similar proportions among HCW who subsequently became infected and those that did not.ConclusionsHCWs in COVID-19 patient care in Sweden have been infected with SARS-CoV-2 at a higher rate compared to blood donors. We demonstrate substantial variation between different IgG-assays and propose that multiple serological targets should be used to verify past infection. Our data suggest that CD4+ T-cell reactivity is not a suitable measure of past infection and does not reliably indicate protection from infection in naive individuals.
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- 2021
10. A truncated glycoprotein G vaccine formulated with Advax-CpG adjuvant provides protection of mice against genital herpes simplex virus 2 infection
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Yoshikazu Honda-Okubo, Tomas Bergström, Jan-Åke Liljeqvist, Nikolai Petrovsky, Malin Bäckström, Staffan Görander, and Jeremy Baldwin
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Sexually transmitted disease ,CpG Oligodeoxynucleotide ,medicine.medical_treatment ,Herpesvirus 2, Human ,Biology ,medicine.disease_cause ,Virus ,Mice ,Immune system ,Viral Envelope Proteins ,Immunity ,medicine ,Animals ,Vaccines ,Herpes Genitalis ,General Veterinary ,General Immunology and Microbiology ,Public Health, Environmental and Occupational Health ,Inulin ,Virology ,Infectious Diseases ,Herpes simplex virus ,Molecular Medicine ,Female ,Adjuvant ,Viral load - Abstract
Herpes simplex virus type 2 (HSV-2) is a common sexually transmitted disease that affects approximately 500 million individuals globally. There is currently no approved vaccine to prevent HSV-2 infection. EXCT4 is a truncated form of the mature glycoprotein G-2 (mgG-2) that unlike full mature form is secreted by expressing cells enabling it to be rapidly scaled up for production. The current study examined whether EXCT4 immunity in mice could be further enhanced through use of adjuvants. EXCT4 formulated with Advax-CpG adjuvant induced a strong Th1-type immune response characterized by interferon gamma (IFN-γ) and protected animals against a lethal genital challenge with HSV-2. This response was associated with reduced viral load in vaginal washes, spinal cord, and dorsal root ganglia. Together the results provide proof of concept that EXCT4 formulated with Advax-CpG adjuvant is a promising HSV-2 vaccine candidate warranting further investigation.
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- 2021
11. Parvovirus B19 in Endomyocardial Biopsy of Patients With Idiopathic Dilated Cardiomyopathy: Foe or Bystander?
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Bert Andersson, Anders Oldfors, Jan-Åke Liljeqvist, Entela Bollano, Magnus Lindh, Kristjan Karason, and Clara Hjalmarsson
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Adult ,Cardiomyopathy, Dilated ,Male ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,Endomyocardial biopsy ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Idiopathic dilated cardiomyopathy ,Parvovirus B19, Human ,Bystander effect ,Humans ,Medicine ,In patient ,Prospective Studies ,030212 general & internal medicine ,Ejection fraction ,biology ,Parvovirus ,business.industry ,Myocardium ,Dilated cardiomyopathy ,Middle Aged ,biology.organism_classification ,medicine.disease ,Transplantation ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Endocardium ,Follow-Up Studies - Abstract
Background Parvovirus B19 (PVB19) has emerged as one of the viruses possibly inducing chronic myocarditis and subsequent idiopathic dilated cardiomyopathy (IDCM). The aim of this work was to investigate the presence and long-term consequences of PVB19-DNA within myocardial biopsies from patients with IDCM and to compare the findings with those from donor hearts (control group). Methods and Results Forty hospitalized IDCM patients (age 47 ± 12 y) with mean left ventricular ejection fraction 27 ± 12% were included. The presence of PVB19-DNA in myocardial biopsies and of IgG and IgM antibodies in patient sera was analyzed. The control group consisted of 20 donor hearts. The follow-up time was 112 ± 57 months. PVB19-DNA was found in myocardial biopsies of both patients (73%) and control samples (55%; P = .25).Three deaths and 8 heart transplantations occurred in the IDCM group, and 6 deaths in the control group (ie, the recipients of the control hearts). No difference in transplantation-free survival between the PVB19-DNA positive/negative IDCM patients or transplant recipients was found. Conclusions PVB19-DNA is a common finding in both patients with IDCM and in healthy donor hearts, not affecting prognosis. These findings support the view that PVB19 is an innocent bystander, frequently found in myocardium with low DNA copies, and not a plausible cause of IDCM.
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- 2019
12. Herpes simplex virus type 2 mucin-like glycoprotein mgg promotes virus release from the surface of infected cells
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Tomas Bergström, Beata Adamiak, Edward Trybala, Marta Bally, Jan-Åke Liljeqvist, Nadia Peerboom, and Malgorzata Krzyzowska
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0301 basic medicine ,Herpesvirus 2, Human ,viruses ,030106 microbiology ,Mutant ,herpes simplex virus type 2 ,medicine.disease_cause ,glycoprotein mgG ,Microbiology ,Virus ,Article ,Microbiology in the medical area ,Glycosaminoglycan ,03 medical and health sciences ,chemistry.chemical_compound ,Viral Envelope Proteins ,Virology ,medicine ,Mikrobiologi inom det medicinska området ,Humans ,Chondroitin sulfate ,single particle analysis ,Cells, Cultured ,Glycoproteins ,chemistry.chemical_classification ,Mucin ,Cell Membrane ,Virion ,Herpes Simplex ,Molecular biology ,Virus Release ,QR1-502 ,030104 developmental biology ,Infectious Diseases ,Herpes simplex virus ,mucin-like protein ,chemistry ,glycosaminoglycans ,Host-Pathogen Interactions ,Mutation ,virus release ,Glycoprotein - Abstract
The contribution of virus components to liberation of herpes simplex virus type 2 (HSV-2) progeny virions from the surface of infected cells is poorly understood. We report that the HSV-2 mutant deficient in the expression of a mucin-like membrane-associated glycoprotein G (mgG) exhibited defect in the release of progeny virions from infected cells manifested by ~2 orders of magnitude decreased amount of infectious virus in a culture medium as compared to native HSV-2. Electron microscopy revealed that the mgG deficient virions were produced in infected cells and present at the cell surface. These virions could be forcibly liberated to a nearly native HSV-2 level by the treatment of cells with glycosaminoglycan (GAG)-mimicking oligosaccharides. Comparative assessment of the interaction of mutant and native virions with surface-immobilized chondroitin sulfate GAG chains revealed that while the mutant virions associated with GAGs ~fourfold more extensively, the lateral mobility of bound virions was much poorer than that of native virions. These data indicate that the mgG of HSV-2 balances the virus interaction with GAG chains, a feature critical to prevent trapping of the progeny virions at the surface of infected cells.
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- 2021
13. Prevalence of viral sexually transmitted infections and HPV high-risk genotypes in women in rural communities in the Department of La Paz, Bolivia
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Jan-Åke Liljeqvist, Katty Terrazas-Aranda, Magnus Lindh, Marianela Patzi-Churqui, and Kristina Eriksson
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0301 basic medicine ,Rural Population ,HBsAg ,High-risk HPV ,Herpesvirus 2, Human ,HIV Infections ,medicine.disease_cause ,Antibodies, Viral ,0302 clinical medicine ,Prevalence ,HBV ,030212 general & internal medicine ,Cervical cancer ,education.field_of_study ,HPV infection ,virus diseases ,La Paz ,HPV-High Risk ,Sexually Transmitted Diseases, Viral ,Middle Aged ,HSV-2 ,Hepatitis B ,Rural communities ,Infectious Diseases ,Female ,medicine.drug ,Research Article ,Adult ,Risk ,Bolivia ,Genotype ,030106 microbiology ,Population ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Young Adult ,medicine ,Sexually transmitted infections ,Seroprevalence ,Humans ,lcsh:RC109-216 ,Women ,Hepatitis B Antibodies ,education ,Hepatitis B virus ,Hepatitis B Surface Antigens ,business.industry ,Gardasil ,Papillomavirus Infections ,HIV ,medicine.disease ,business ,Demography - Abstract
Background Bolivia has the highest prevalence of cervical cancer in South America and the prevalence of viral sexually transmitted infections (STIs) among people in urban cities is increasing. Little is known about the prevalence of viral STIs in rural communities, which generally have limited access to health care. In order to study the prevalence of viral STIs in rural Bolivia, we recruited women from villages and towns in the Department of La Paz in Bolivia. Methods Three hundred ninety-four female participants were assessed for IgG-antibodies to herpes simplex virus type 2 (HSV-2), human immunodeficiency virus (HIV) and hepatitis B virus (HBV, anti-HBc), as well as for the presence of HBV surface antigen (HBsAg) in dried blood spots. The prevalence of 12 high-risk types of human papillomavirus (HPV) was assessed by qPCR in dried cervicovaginal cell spots from 376 of these women. χ2 test was used to compare variables between the populations and binary logistic regression was used to identify risk factors associated with the positivity of the tests. Results The seroprevalence of HSV-2 was 53% and of HBV 10.3%. HBAg was detected in 15.8% of women with anti-HBV antibodies indicating chronic infection. The frequency of high-risk HPV infection was 27%, with the most prevalent high-risk HPV types being HPV 56, 39 and 31 followed by HPV 16 and 18. Finally, none of the 394 women were seropositive for HIV, and about 64% of the studied population was positive for at least one of the viral infections. Conclusions Women in Bolivian rural communities in La Paz show a high prevalence of HBV, HPV and, in particular, HSV-2. In contrast, none of the women were HIV positive, suggesting that the HIV prevalence in this population is low. The pattern of high-risk HPV types differed from many other countries with a predominance of HPV-types not included in the Gardasil vaccine which was officially introduced in Bolivia in April 2017.
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- 2020
14. Cytomegalovirus Serostatus Affects Autoreactive NK Cells and Outcomes of IL2-Based Immunotherapy in Acute Myeloid Leukemia
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Malin Nicklasson, Malin S Nilsson, Robin Foà, Frida Ewald Sander, Kristoffer Hellstrand, Mats Brune, Karin Christenson, Elin Bernson, Fredrik B. Thorén, Johan Aurelius, Alexander Hallner, Anna Martner, Ebru Aydin, and Jan-Åke Liljeqvist
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Adult ,Male ,0301 basic medicine ,Human cytomegalovirus ,Cancer Research ,Adolescent ,medicine.medical_treatment ,Immunology ,Population ,Cytomegalovirus ,Human leukocyte antigen ,Antibodies, Viral ,Young Adult ,03 medical and health sciences ,Receptors, KIR ,HLA Antigens ,medicine ,Humans ,education ,Aged ,education.field_of_study ,business.industry ,virus diseases ,Myeloid leukemia ,Immunotherapy ,Middle Aged ,medicine.disease ,Killer Cells, Natural ,Transplantation ,Leukemia, Myeloid, Acute ,030104 developmental biology ,Cytomegalovirus Infections ,Interleukin-2 ,Female ,Stem cell ,business ,Serostatus ,Histamine - Abstract
Human cytomegalovirus (CMV) infection is reported to promote NK cell differentiation and education. The CMV-induced generation of highly differentiated adaptive-like NK cells has been proposed to affect favorably on the maintenance of remission in patients with acute myeloid leukemia (AML) after allogeneic stem cell transplantation (allo-SCT). The impact of CMV infection and adaptive-like NK cells on relapse and survival of patients with AML not receiving allo-SCT remains unknown. We assayed CMV IgG serostatus to determine past CMV infection in 81 nontransplanted AML patients who were receiving relapse-prevention immunotherapy comprising histamine dihydrochloride and low-dose interleukin-2 (HDC/IL2; NCT01347996). CMV seropositivity correlated negatively with leukemia-free and overall survival of patients receiving HDC/IL2, but did not correlate with outcomes in a contemporary control cohort. Analysis of outcome after stratification of patients based on concordant or discordant killer immunoglobulin-like receptor (KIR) and HLA genotypes implied that the negative impact of CMV seropositivity was restricted to patients lacking a ligand to inhibitory KIRs (iKIR). Previous CMV infection was also associated with fewer NK cells expressing only nonself iKIRs (NS-iKIR). We propose that CMV-driven NK cell education depletes the population of NS-iKIR NK cells, which in turn reduces the clinical benefit of relapse-preventive immunotherapy in AML. Cancer Immunol Res; 6(9); 1110–9. ©2018 AACR.
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- 2018
15. Prevalence of viral sexually transmitted infections and HPV high-risk genotypes in women in rural communities in Bolivia
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Kristina Eriksson, Jan-Åke Liljeqvist, Marianela Patzi-Churqui, Katty Terrazas-Aranda, and Magnus Lindh
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business.industry ,Genotype ,virus diseases ,Medicine ,HPV-High Risk ,business ,Demography - Abstract
Background: Bolivia has the highest prevalence of cervical cancer in South America and the prevalence of viral sexually transmitted infections (STIs) among people in urban cities is increasing. Little is known about the prevalence of viral STIs in rural communities, which generally have limited access to health care. In order to study the prevalence of viral STIs in rural Bolivia, we recruited women from villages and towns in the Department of La Paz in Bolivia. Methods: 394 female participants were assessed for IgG-antibodies to herpes simplex virus type 2 (HSV-2), human immunodeficiency virus (HIV) and hepatitis B virus (HBV, anti-HBc), as well as for the presence of HBV surface antigen (HBsAg) in dried blood spots. The prevalence of 12 high-risk types of human papillomavirus (HPV) was assessed by qPCR in dried cervicovaginal cell spots from 376 of these women. χ 2 test was used to compare variables between the populations and binary logistic regression was used to identify risk factors associated with the positivity of the tests. Results: The seroprevalence of HSV-2 was 53% and of HBV 10.3%. HBAg was detected in 15.8% of women with anti-HBV antibodies indicating chronic infection. The frequency of high-risk HPV infection was 27%, with the most prevalent high-risk HPV types being HPV 56, 39 and 31 followed by HPV 16 and 18. Finally, none of the 394 women were seropositive for HIV, and about 64% of the studied population was positive for at least one of the viral infections. Conclusions: Women in Bolivian rural communities in La Paz show a high prevalence of HBV, HPV and, in particular, HSV-2, but a low prevalence of HIV. The pattern of high-risk HPV types differed from e.g. Sweden with a predominance of HPV-types not included in the Gardasil vaccine which was officially introduced in Bolivia in April 2017.
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- 2019
16. Measles outbreak in Gothenburg urban area, Sweden, 2017 to 2018: low viral load in breakthrough infections
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Tobias Tyrberg, Lars-Magnus Andersson, Marie Studahl, Martina Sansone, Leif Dotevall, Jan-Åke Liljeqvist, Nicklas Sundell, Maria Andersson, Magnus Lindh, Johan Westin, Tomas Bergström, and Thomas Wahlberg
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Male ,Pediatrics ,Letter ,Urban Population ,Epidemiology ,serology ,Antibodies, Viral ,Disease Outbreaks ,Serology ,fluids and secretions ,Nasopharynx ,vaccine ,Medicine ,measles transmission ,Child ,Transmission (medicine) ,Medical record ,Vaccination ,virus diseases ,breakthrough cases ,Middle Aged ,Viral Load ,vaccinated cases ,PCR ,Child, Preschool ,Female ,Viral load ,Adult ,endocrine system ,medicine.medical_specialty ,Adolescent ,Genotype ,Measles Vaccine ,Real-Time Polymerase Chain Reaction ,complex mixtures ,Measles ,Young Adult ,Virology ,parasitic diseases ,Humans ,measles ,Serologic Tests ,Sweden ,outbreak ,business.industry ,Infant, Newborn ,Outbreaks ,Public Health, Environmental and Occupational Health ,Infant ,Outbreak ,medicine.disease ,immunity ,Immunoglobulin M ,Measles virus ,Immunoglobulin G ,business ,Contact tracing - Abstract
In an outbreak of measles in Gothenburg, Sweden, breakthrough infections (i.e. infections in individuals with a history of vaccination) were common. The objective of this study was to compare measles RNA levels between naïve (i.e. primary) and breakthrough infections. We also propose a fast provisional classification of breakthrough infections. Medical records were reviewed and real-time PCR-positive samples genotyped. Cases were classified as naïve, breakthrough or vaccine infections. We compared clinical symptoms and measles RNA cycle threshold (Ct) values between breakthrough and naïve infections. Sixteen of 28 confirmed cases of measles in this outbreak were breakthrough infections. A fast provisional classification, based on previous history of measles vaccination and detectable levels of measles IgG in acute serum, correctly identified 14 of the 16 breakthrough infections, confirmed by IgG avidity testing. Measles viral load was significantly lower in nasopharyngeal samples from individuals with breakthrough compared with naïve infections (median Ct-values: 32 and 19, respectively, p
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- 2019
17. Authors’ response: Measles outbreak in Gothenburg urban area, Sweden, 2017/18: lower viral load in breakthrough infections
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Johan Westin, Tomas Bergström, Marie Studahl, Magnus Lindh, Lars-Magnus Andersson, Leif Dotevall, Jan-Åke Liljeqvist, and Nicklas Sundell
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Letter ,Epidemiology ,Measles outbreak ,serology ,Urban area ,Measles ,Serology ,Disease Outbreaks ,Virology ,Environmental health ,vaccine ,Medicine ,measles ,Humans ,Serologic Tests ,Sweden ,geography ,geography.geographical_feature_category ,outbreak ,business.industry ,Public Health, Environmental and Occupational Health ,Outbreak ,Viral Load ,medicine.disease ,immunity ,PCR ,business ,Viral load - Published
- 2019
18. The Cholestanol-Conjugated Sulfated Oligosaccharide PG545 Disrupts the Lipid Envelope of Herpes Simplex Virus Particles
- Author
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Stefan Lange, Maria Ekblad, Eva Jennische, Joanna Said, Staffan Görander, Edward Trybala, Jan-Åke Liljeqvist, and Tomas Bergström
- Subjects
0301 basic medicine ,Herpesvirus 2, Human ,viruses ,Oligosaccharides ,Biology ,Polysaccharide ,medicine.disease_cause ,Antiviral Agents ,Virus ,Glycosaminoglycan ,03 medical and health sciences ,Sulfation ,Viral envelope ,medicine ,Animals ,Pharmacology (medical) ,Pharmacology ,chemistry.chemical_classification ,Herpes Genitalis ,Vaginal microbicide ,Virion ,Saponins ,Oligosaccharide ,Lipids ,Virology ,Mice, Inbred C57BL ,Administration, Intravaginal ,Disease Models, Animal ,030104 developmental biology ,Infectious Diseases ,Herpes simplex virus ,chemistry ,Female - Abstract
Herpes simplex virus (HSV) and many other viruses, including HIV, initiate infection of host cells by binding to glycosaminoglycan (GAG) chains of cell surface proteoglycans. Although GAG mimetics, such as sulfated oligo- and polysaccharides, exhibit potent antiviral activities in cultured cells, the prophylactic application of these inhibitors as vaginal microbicides failed to protect women upon their exposure to HIV. A possible explanation for this failure is that sulfated oligo- and polysaccharides exhibit no typical virucidal activity, as their interaction with viral particles is largely electrostatic and reversible and thereby vulnerable to competition with GAG-binding proteins of the genital tract. Here we report that the cholestanol-conjugated sulfated oligosaccharide PG545, but not several other sulfated oligosaccharides lacking this modification, exhibited virucidal activity manifested as disruption of the lipid envelope of HSV-2 particles. The significance of the virus particle-disrupting activity of PG545 was also demonstrated in experimental animals, as this compound, in contrast to unmodified sulfated oligosaccharide, protected mice against genital infection with HSV-2. Thus, PG545 offers a novel prophylaxis option against infections caused by GAG-binding viruses.
- Published
- 2016
19. Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders
- Author
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Helene Norder, Aylin Yilmaz, Staffan Nilsson, Jan-Åke Liljeqvist, Kristina Nyström, Lars-Magnus Andersson, Mats Bemark, Davide Angeletti, Anna Lundgren, Magnus Gisslén, Emelie Marklund, Hannes Axelsson, Susannah Leach, and Magnus Lindh
- Subjects
RNA viruses ,0301 basic medicine ,Viral Diseases ,Coronaviruses ,Physiology ,Antibody Response ,Pathology and Laboratory Medicine ,Biochemistry ,Gastroenterology ,Immunoglobulin G ,Serology ,Medical Conditions ,Spectrum Analysis Techniques ,0302 clinical medicine ,Immune Physiology ,Blood Flow ,Medicine and Health Sciences ,Medicine ,030212 general & internal medicine ,Enzyme-Linked Immunoassays ,Immune Response ,Immune System Proteins ,Multidisciplinary ,biology ,Antibody titer ,Medical microbiology ,Flow Cytometry ,Body Fluids ,Infectious Diseases ,Blood ,Spectrophotometry ,Viruses ,Cohort ,Cytophotometry ,SARS CoV 2 ,Pathogens ,Anatomy ,Antibody ,Research Article ,medicine.medical_specialty ,SARS coronavirus ,Coronavirus disease 2019 (COVID-19) ,Science ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunology ,Research and Analysis Methods ,Microbiology ,Antibodies ,03 medical and health sciences ,Immunity ,Internal medicine ,Severity of illness ,Seroprevalence ,Seroconversion ,Immunoassays ,Biology and life sciences ,business.industry ,Organisms ,Viral pathogens ,Proteins ,Covid 19 ,Seroepidemiologic Studies ,Microbial pathogens ,030104 developmental biology ,Immunologic Techniques ,biology.protein ,business - Abstract
BackgroundTo accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset.ResultsForty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P=0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset.ConclusionsPatients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys and for estimating the true infection prevalence in populations.
- Published
- 2020
20. Anti-Glycoprotein G Antibodies of Herpes Simplex Virus 2 Contribute to Complete Protection after Vaccination in Mice and Induce Antibody-Dependent Cellular Cytotoxicity and Complement-Mediated Cytolysis
- Author
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Maria Ekblad, Tomas Bergström, Staffan Görander, and Jan-Åke Liljeqvist
- Subjects
CD4-Positive T-Lymphocytes ,glycoprotein G ,medicine.drug_class ,Herpesvirus 2, Human ,Injections, Subcutaneous ,medicine.medical_treatment ,lcsh:QR1-502 ,chemical and pharmacologic phenomena ,Antibodies, Viral ,Monoclonal antibody ,Injections, Intramuscular ,Article ,lcsh:Microbiology ,Immunoglobulin G ,Interferon-gamma ,Adjuvants, Immunologic ,Viral Envelope Proteins ,Virology ,Animals ,antibodies ,Medicine ,Cell Proliferation ,Antibody-dependent cell-mediated cytotoxicity ,biology ,business.industry ,Antibody-Dependent Cell Cytotoxicity ,Immunization, Passive ,Herpes Simplex Virus Vaccines ,Herpes Simplex ,Complement System Proteins ,vaccination ,Survival Analysis ,Mice, Inbred C57BL ,Vaccination ,Cytolysis ,Infectious Diseases ,Immunization ,Immunology ,biology.protein ,Female ,Antibody ,business ,herpes simplex virus 2 ,Adjuvant - Abstract
We investigated the role of antibodies against the mature portion of glycoprotein G (mgG-2) of herpes simplex virus 2 (HSV-2) in protective immunity after vaccination. Mice were immunized intramuscularly with mgG-2 and oligodeoxynucleotides containing two CpG motifs plus alum as adjuvant. All C57BL/6 mice survived and presented no genital or systemic disease. High levels of immunoglobulin G subclass 1 (IgG1) and IgG2 antibodies were detected and re-stimulated splenic CD4+ T cells proliferated and produced IFN-γ. None of the sera from immunized mice exhibited neutralization, while all sera exerted antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytolysis (ACMC) activity. Passive transfer of anti-mgG-2 monoclonal antibodies, or immune serum, to naive C57BL/6 mice did not limit disease progression. Immunized B‑cell KO mice presented lower survival rate and higher vaginal viral titers, as compared with vaccinated B-cell KO mice after passive transfer of immune serum and vaccinated C57BL/6 mice. Sera from mice that were vaccinated subcutaneously and intranasally with mgG-2 presented significantly lower titers of IgG antibodies and lower ADCC and ACMC activity. We conclude that anti-mgG-2 antibodies were of importance to limit genital HSV‑2 infection. ADCC and ACMC activity are potentially important mechanisms in protective immunity, and could tentatively be evaluated in future animal vaccine studies and in clinical trials.
- Published
- 2014
21. Herpes simplex virus specific T cell response in a cohort with primary genital infection correlates inversely with frequency of subsequent recurrences
- Author
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Hans Gaines, Louise Berg, Arne Wikström, Tomas Bergström, Fredrik Atterfelt, Elisabeth Franzen-Röhl, Klas Kärre, Danika Schepis, Kristina Franck, Elisabeth Aurelius, and Jan-Åke Liljeqvist
- Subjects
0301 basic medicine ,viruses ,Herpesvirus 2, Human ,T-Lymphocytes ,Mucocutaneous zone ,Dermatology ,Herpesvirus 1, Human ,medicine.disease_cause ,Serology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Infection control ,Medicine ,Humans ,Sex organ ,030212 general & internal medicine ,First episode ,Herpes Genitalis ,business.industry ,medicine.disease ,030104 developmental biology ,Infectious Diseases ,Herpes simplex virus ,Cohort ,Immunology ,business ,Meningitis - Abstract
Objectives During the last decades, a changing epidemiological pattern of genital herpes simplex virus (HSV) infection has emerged. Primary infection is now caused as often by HSV-1 as by HSV-2. Once established, HSV can be reactivated leading to recurrent mucocutaneous lesions as well as meningitis. Why some otherwise immune-competent individuals experience severe and frequent recurrences is not known, and the immunological mechanism underlying recurrent symptomatic HSV infection is not fully understood. In this study, we investigate and characterise the immune response of patients with first episode of HSV genital infection and its relation to the frequency of symptomatic recurrences. Methods In this cohort study, clinical and immunological data were collected from 29 patients who were followed 1 year after presenting with a first episode of genital or meningeal HSV infection. They were classified by PCR and serology as those with primary HSV-1, primary HSV-2 and non-primary HSV-2 infection. Results HSV-specific interleukin(Il)-4 and Il-10 responses at first visit were higher in primary infected HSV-2 infected patients experiencing lower numbers of recurrences during subsequent year. Conclusions The median number of recurrences following primary HSV-2 genital infection may partly be predicted by the strength of an early HSV-specific IL-4 and IL-10 response.
- Published
- 2016
22. Glycoprotein G of Herpes Simplex Virus 2 as a Novel Vaccine Antigen for Immunity to Genital and Neurological Disease
- Author
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Madelene Lindqvist, Tomas Bergström, Ali M. Harandi, Jan-Åke Liljeqvist, and Staffan Görander
- Subjects
CD4-Positive T-Lymphocytes ,Herpesvirus 2, Human ,medicine.medical_treatment ,Immunology ,Biology ,medicine.disease_cause ,Microbiology ,Cell Line ,Interferon-gamma ,Mice ,Adjuvants, Immunologic ,Viral Envelope Proteins ,Antigen ,Immunity ,Cricetinae ,Virology ,Chlorocebus aethiops ,Vaccines and Antiviral Agents ,medicine ,Animals ,Interferon gamma ,Herpes Simplex Virus Vaccines ,Herpes Genitalis ,Macrophages ,Viral Vaccine ,Antibody-Dependent Cell Cytotoxicity ,Herpes Simplex ,Viral Vaccines ,Mice, Inbred C57BL ,Herpes simplex virus ,Spinal Cord ,CpG site ,Insect Science ,Vagina ,CpG Islands ,Female ,Immunization ,Nervous System Diseases ,Adjuvant ,medicine.drug - Abstract
The envelope glycoproteins of herpes simplex virus 1 (HSV-1) and HSV-2, with the exception of glycoprotein G, elicit cross-reactive B- and T-cell responses. Human vaccine trials, using the cross-reactive glycoproteins B and D, have shown no protection against genital HSV-2 infection or disease. In this study, the mature form of glycoprotein G (mgG-2) of HSV-2 was used for immunization of mice, either alone or in combination with adjuvant CpG, followed by an intravaginal challenge with a lethal dose of a fully virulent HSV-2 strain. Mice immunized with mgG-2 plus CpG showed low disease scores and a significantly higher survival rate (73%) than mice immunized with mgG-2 alone (20%) or controls (0%). Accordingly, limited numbers of infectious HSV-2 particles were detected in the spinal cord of mice immunized with mgG-2 plus CpG. The observed protection was associated with a gamma interferon (IFN-γ) response by splenic CD4 + T cells upon antigen restimulation in vitro and in vaginal washes 1 day postinfection. The majority of sera collected from mice immunized with mgG-2 plus CpG showed macrophage-mediated antibody-dependent cellular cytotoxicity and antibody-dependent complement-mediated cytolysis, while no neutralization activity was observed. In conclusion, we have shown that immunization with the type-specific mgG-2 protein in combination with CpG could elicit protective immunity against an otherwise lethal vaginal HSV-2 challenge. The mgG-2 protein may therefore constitute a promising HSV-2 vaccine antigen to be considered for future human trials.
- Published
- 2012
23. Increased Cell-Mediated Immune Responses in Patients with Recurrent Herpes Simplex Virus Type 2 Meningitis
- Author
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Tomas Bergström, Kristina Franck, Hans Gaines, Elisabeth Franzen-Röhl, Klas Kärre, Maria Lagrelius, Danika Schepis, Jan-Åke Liljeqvist, Louise Berg, Elisabeth Aurelius, and Petra Jones
- Subjects
Adult ,Male ,Microbiology (medical) ,Herpesvirus 2, Human ,T-Lymphocytes ,viruses ,T cell ,Clinical Biochemistry ,Immunology ,Gene Expression ,Alpha interferon ,Biology ,medicine.disease_cause ,Immune system ,Recurrence ,medicine ,Humans ,Immunology and Allergy ,Immunity, Cellular ,Innate immune system ,Toll-Like Receptors ,Herpes Simplex ,Dendritic Cells ,Dendritic cell ,Middle Aged ,medicine.disease ,Meningitis, Viral ,Virology ,Killer Cells, Natural ,Herpes simplex virus ,medicine.anatomical_structure ,Cytokines ,Female ,Cytokine secretion ,Microbial Immunology ,Meningitis - Abstract
The clinical picture of herpes simplex virus type 2 (HSV-2) infection includes genital blisters and less frequently meningitis, and some individuals suffer from recurrent episodes of these manifestations. We hypothesized that adaptive and/or innate immune functional deficiencies may be a major contributing factor in susceptibility to recurrent HSV-2 meningitis. Ten patients with recurrent HSV-2 meningitis were studied during clinical remission. For comparison, 10 patients with recurrent genital HSV infections as well as 21 HSV-seropositive and 19 HSV-seronegative healthy blood donors were included. HSV-specific T cell blasting and cytokine secretion were evaluated in whole blood cultures. HSV-2-induced NK cell gamma interferon production, dendritic cell Toll-like receptor (TLR) expression, and TLR agonist-induced alpha interferon secretion were analyzed. Patients with recurrent HSV-2 meningitis had elevated T cell blasting and Th1 and Th2 cytokine production in response to HSV antigens compared to those of patients with recurrent genital infections. A somewhat increased NK cell response, increased dendritic cell expression of TLR3 and -9, and increased TLR-induced alpha interferon responses were also noted. Contrary to our expectation, recurrent HSV-2 meningitis patients have increased HSV-specific adaptive and innate immune responses, raising the possibility of immune-mediated pathology in the development of recurrent HSV2 meningitis.
- Published
- 2011
24. Infection of infants with human herpesvirus type 6 may be associated with reduced allergic sensitization and T-helper type 2 development
- Author
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Anna Rudin, Bill Hesselmar, Robert Saalman, Ingegerd Adlerberth, Agnes E. Wold, Inger Nordström, Nils Åberg, Kristina Eriksson, and Jan-Åke Liljeqvist
- Subjects
Allergy ,biology ,Immunology ,biology.organism_classification ,Immunoglobulin E ,medicine.disease ,Virology ,Allergic sensitization ,Immune system ,Cord blood ,Interleukin 13 ,biology.protein ,medicine ,Immunology and Allergy ,Human herpesvirus 6 ,Interleukin 5 - Abstract
Summary Background Epidemiological studies point to an inverse relationship between microbial exposure and the prevalence of allergic diseases. The underlying mechanism for this observation remains largely unknown, as well as the nature of the microbes involved. Objective To investigate the effects of early infection with human herpesviruses (HHVs) on IgE formation and T-helper type 2 (Th2) development in infants. Methods Serum was collected from children aged 18 months and assessed for IgE to common allergens and IgG to five common herpesviruses. Cord blood plasmacytoid dendritic cells (pDC) were exposed to HHV type 6 in vitro and mixed with allogeneic cord blood CD4+ T cells. Cytokine levels were determined by ELISA and by flow cytometry. Results We found that children seropositive at 18 months of age to HHV type 6 were significantly less often IgE sensitized than seronegative children [odds ratio (OR): 0.08, 95% confidence interval (CI): 0.009–0.68]. HHV type 6 also decreased the production of the Th2-associated cytokines IL-5 and IL-13 by CD4+ T cells when co-cultured with allogeneic cord blood pDC. This was associated with an increased production of IFN-α by pDC exposed to HHV type 6. Conclusion These data indicate that an early childhood infection with HHV type 6 could down-regulate Th2 responses and reduce IgE formation to common allergens in a young child.
- Published
- 2010
25. Asymptomatically shed recombinant herpes simplex virus type 1 strains detected in saliva
- Author
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Jan Åke Liljeqvist, Petra Tunbäck, and Peter Norberg
- Subjects
Adult ,Male ,Saliva ,Adolescent ,viruses ,Herpesvirus 1, Human ,Biology ,medicine.disease_cause ,Recombinant virus ,Virus ,law.invention ,law ,Virology ,Genetic variation ,medicine ,Humans ,Viral shedding ,Child ,Phylogeny ,Polymerase chain reaction ,Recombination, Genetic ,Herpes Simplex ,Sequence Analysis, DNA ,Virus Shedding ,Herpes simplex virus ,DNA, Viral ,Recombinant DNA ,Female - Abstract
Herpes simplex virus type 1 (HSV-1) is a ubiquitous pathogen infecting most individuals worldwide. The majority of HSV-1-infected individuals have no clinical symptoms but shed HSV-1 asymptomatically in saliva. Recent phylogenetic analyses of HSV-1 have defined three genetic clades (A–C) and recombinants thereof. These data have all been based on clinical HSV-1 isolates and do not cover genetic variation of asymptomatically shed HSV-1. The primary goal of this study was to investigate such variation. A total of 648 consecutive saliva samples from five HSV-1-infected volunteers was collected. Asymptomatic shedding was detected on 7.6 % of the days from four subjects. The HSV-1 genome loads were quantified with real-time PCR and varied from 1×102to 2.8×106 copies of virus DNA (ml saliva)−1. Phylogenetic network analyses and bootscanning were performed on asymptomatically shed HSV-1. The analyses were based on DNA sequencing of the glycoprotein I gene, and also of the glycoprotein E gene for putative recombinants. For two individuals with clinical HSV-1 infection, the same HSV-1 strain was shed asymptomatically as induced clinical lesions, and sequence analyses revealed that these strains clustered distinctly to clades A and B, respectively. For one of the subjects with no clinical HSV-1 infection, a recombinant strain was identified. The other truly asymptomatic individual shed evolutionarily distinct HSV-1 strains on two occasions. The first strain was classified as a recombinant and the other strain clustered in clade A. High replication rates of different strains in the same person may facilitate the creation of recombinant clinical HSV-1 strains.
- Published
- 2009
26. Seroprevalences of Herpes Simplex Virus Type 2, Five Oncogenic Human Papillomaviruses, and Chlamydia trachomatis in Katowice, Poland
- Author
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Teresa Lagergård, Gayane Martirosian, Małgorzata Romanik, Staffan Görander, Raphael P. Viscidi, and Jan Åke Liljeqvist
- Subjects
Adult ,Male ,Microbiology (medical) ,Herpesvirus 2, Human ,Clinical Biochemistry ,Immunology ,Chlamydia trachomatis ,HPV vaccines ,medicine.disease_cause ,Immunoglobulin G ,Seroepidemiologic Studies ,medicine ,Humans ,Immunology and Allergy ,Papillomaviridae ,Herpes Genitalis ,biology ,Papillomavirus Infections ,virus diseases ,Chlamydia Infections ,Middle Aged ,biology.organism_classification ,Virology ,female genital diseases and pregnancy complications ,Herpes simplex virus ,Cohort ,biology.protein ,Female ,Poland ,Microbial Immunology ,Antibody - Abstract
Herpes simplex virus type 2 (HSV-2), human papillomaviruses (HPVs), and Chlamydia trachomatis are the most common pathogens causing sexually transmitted infections (STIs). There is limited information about the prevalences of these STIs in Poland. Here, we estimated the occurrence of immunoglobulin G (IgG) antibodies against HSV-2, HPV, and C. trachomatis in 199 blood donors and 110 patients of both genders attending an STI clinic in Katowice in southern Poland. The seroprevalences of HSV-2 were 5% for blood donors and 14% in the STI cohort. The seroprevalences of the five potentially oncogenic HPV types 16, 18, 31, 35, and 51 were 15%, 7%, 5%, 5%, and 17%, respectively, in blood donors and 37%, 8%, 12%, 5%, and 21%, respectively, in the STI cohort. The majority of HPV-infected individuals showed antibodies against more than one type, i.e., had been infected with multiple HPV types. Anti- C. trachomatis IgG antibodies were detected in 6% of blood donors and 13% of individuals attending the STI clinic. The relatively high prevalence of HPV-51 may have implications for future vaccine programs, as the newly introduced HPV vaccines are based on the potentially oncogenic HPV types 16 and 18.
- Published
- 2008
27. Glycoprotein I of herpes simplex virus type 1 contains a unique polymorphic tandem-repeated mucin region
- Author
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Sigvard Olofsson, Jan Åke Liljeqvist, Mads Agervig Tarp, Peter Norberg, Tomas Bergström, and Henrik Clausen
- Subjects
chemistry.chemical_classification ,Glycosylation ,Polymorphism, Genetic ,Immunoblotting ,Tn antigen ,Herpesvirus 1, Human ,Biology ,medicine.disease_cause ,Virology ,Molecular biology ,Virus ,Amino acid ,carbohydrates (lipids) ,Serine ,Herpes simplex virus ,Viral Envelope Proteins ,Tandem repeat ,chemistry ,Tandem Repeat Sequences ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,medicine ,N-Acetylgalactosaminyltransferases ,Threonine ,Glycoprotein - Abstract
Glycoprotein I (gI) of herpes simplex virus type 1 (HSV-1) contains a tandem repeat (TR) region including the amino acids serine and threonine, residues that can be utilized forO-glycosylation. The length of this TR region was determined for 82 clinical HSV-1 isolates and the results revealed a polymorphic distribution of two to six or eight repeated blocks with a majority harbouring between two and four repeats. Assessment of theO-glycosylation capacity of an acceptor peptide (STPSTTTSTPSTTT), representing two of the gI blocks, showed that the peptide was a universal substrate forO-glycosylation not only for the two most commonly expressedN-acetyl-d-galactosamine (GalNAc)-T1 and -T2 transferases, but also for the GalNAc-T3, -T4 and -T11 transferases. Immunoblotting of virus-infected cells showed that gI was exclusivelyO-glycosylated with GalNAc monosaccharides (Tn antigen). A polymorphic mucin region has not been described previously for HSV-1 and is a unique finding, as repeated blocks within gI homologues are lacking in other alphaherpesviruses.
- Published
- 2007
28. Microglial GLT-1 is upregulated in response to herpes simplex virus infection to provide an antiviral defence via glutathione
- Author
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Jan-Åke Liljeqvist, Mikael Persson, Mona Brantefjord, Tomas Bergström, Lars Rönnbäck, and Elisabeth Hansson
- Subjects
Herpesvirus 2, Human ,viruses ,Central nervous system ,Cell ,Glutamic Acid ,Herpesvirus 1, Human ,Biology ,medicine.disease_cause ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Downregulation and upregulation ,medicine ,Animals ,Cells, Cultured ,Microglia ,Tumor Necrosis Factor-alpha ,Brain ,Glutathione ,medicine.disease ,Virology ,Immunity, Innate ,Rats ,Up-Regulation ,Herpes simplex virus ,medicine.anatomical_structure ,Animals, Newborn ,Excitatory Amino Acid Transporter 2 ,Neurology ,chemistry ,Tumor necrosis factor alpha ,Encephalitis, Herpes Simplex ,Encephalitis - Abstract
Herpes simplex virus (HSV) can enter the central nervous system and cause encephalitis (HSV-1) or meningitis (HSV-2). Microglia, the immunocompetent cells of the central nervous system, are potentially able to detect viral infections. Microglia have been shown to express the glutamate transporter GLT-1 during pathological events, leading to increased microglial glutamate uptake and glutathione synthesis. This study aims to address the role of GLT-1 and glutathione, a major antioxidant with antiviral properties, during HSV infections. Using neuron-enriched mixed primary cultures from rat, it was found that microglia have higher resistance to HSV infections than neurons or astrocytes after 24 h incubation with HSV. Purified microglia in culture were used to further address this. It was found that microglia were able to detect HSV and responded by releasing tumor necrosis factor-alpha (TNF-alpha) and upregulating GLT-1 after 24 h incubation with 1 PFU/cell HSV-1 or HSV-2. Furthermore, the microglial glutathione levels were not significantly diminished after 24 h. Inhibition of the microglial glutathione synthesis with 200 microM buthionine sulfoximide (BSO) led to significantly more infected cells after 24 h incubation with 1 PFU/cell HSV-1 or HSV-2. These data indicate that the higher resistance in microglia against HSV infections may be due to the expression of GLT-1, which can maintain the glutathione levels and provide a mechanism for microglial self-defense against HSV.
- Published
- 2007
29. Genotyping of Clinical Herpes Simplex Virus Type 1 Isolates by Use of Restriction Enzymes
- Author
-
Jan-Åke Liljeqvist, Tomas Bergström, and Peter Norberg
- Subjects
Microbiology (medical) ,Genotype ,viruses ,Herpesvirus 1, Human ,Biology ,medicine.disease_cause ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Virus ,law.invention ,Viral Envelope Proteins ,law ,Virology ,medicine ,Cluster Analysis ,Humans ,Typing ,Genotyping ,Polymerase chain reaction ,Genetics ,Herpes Simplex ,DNA Restriction Enzymes ,DNA Fingerprinting ,Restriction enzyme ,Herpes simplex virus ,DNA profiling ,DNA, Viral ,Polymorphism, Restriction Fragment Length - Abstract
Recently, three distinct genotypes of clinical herpes simplex virus type 1 (HSV-1) isolates were identified based on DNA sequence information and phylogenetic analysis of clinical isolates and laboratory strains. We utilized single-nucleotide polymorphism within the genes coding for glycoproteins G and I for rapid genotype classification by PCR and restriction enzyme cleavage. The method is suitable for high-scale genotyping of clinical HSV-1 isolates and for the detection of recombinants.
- Published
- 2006
30. Mature Glycoprotein G Presents High Performance in Diagnosing Herpes Simplex Virus Type 2 Infection in Sera of Different Tanzanian Cohorts
- Author
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Jan-Åke Liljeqvist, Staffan Görander, Judica Mbwana, Eligius Lyamuya, and Teresa Lagergård
- Subjects
Adult ,Male ,Microbiology (medical) ,medicine.medical_specialty ,Adolescent ,Herpesvirus 2, Human ,Blotting, Western ,Clinical Biochemistry ,Immunology ,Enzyme-Linked Immunosorbent Assay ,Biology ,Infections ,medicine.disease_cause ,Sensitivity and Specificity ,Tanzania ,Cohort Studies ,Sex Factors ,Viral Envelope Proteins ,Antigen ,Antibody Specificity ,Seroepidemiologic Studies ,Epidemiology ,medicine ,Animals ,Humans ,Immunology and Allergy ,Seroprevalence ,Herpes Genitalis ,Cells, Cultured ,Age Factors ,Middle Aged ,Virology ,Herpes simplex virus ,Cohort ,Female ,Microbial Immunology ,Cohort study - Abstract
Herpes simplex virus type 2 (HSV-2) is a common sexually transmitted infection in sub-Saharan Africa. Glycoprotein G (gG) of HSV-2 elicits a type-specific antibody response and is widely used for serodiagnosis. gG is cleaved into a secreted portion (sgG-2) and a highly O-glycosylated mature portion (mgG-2). The performances of these two native immunosorbent purified antigens were compared in an enzyme-linked immunosorbent assay (ELISA) format with a commercially available assay (FOCUS2) using sera from blood donors ( n = 194) and individuals ( n = 198) with genital ulcer disease (GUD) from Tanzania. Discordant results were resolved by Western blotting. The HSV-2 seroprevalence for blood donors was estimated as 42%, and that for the GUD cohort was estimated as 78%. The prevalence increased significantly with age for both cohorts and was higher among human immunodeficiency virus (HIV)-positive individuals than among HIV-negative subjects. In the GUD cohort with a high HSV-2 prevalence, all three assays showed statistically similar performances, with sensitivities between 97% and 99% and specificities in the range of 86% to 91%. In contrast, among blood donors with a lower seroprevalence, the mgG-2-based ELISA presented significantly higher specificity (97%) than the sgG-2 ELISA (89%) and FOCUS2 (74%). Overall, the mgG-2 ELISA gave a high performance, with negative and positive predictive values of 96% for blood donors and a negative predictive value of 95% and a positive predictive value of 97% for the GUD cohort. We conclude that native purified mgG-2 showed the highest accuracy for detection of HSV-2 in patient sera from Tanzania and is therefore suitable for seroprevalence studies as well as in clinical settings.
- Published
- 2006
31. CD4+ T-cell responses to herpes simplex virus type 2 (HSV-2) glycoprotein G are type specific and differ in symptomatic and asymptomatic HSV-2-infected individuals
- Author
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Staffan Görander, Lars Bellner, Petra Tunbäck, Jan-Åke Liljeqvist, Kristina Rydberg, Gun-Britt Löwhagen, and Kristina Eriksson
- Subjects
Adult ,CD4-Positive T-Lymphocytes ,Male ,Cellular immunity ,viruses ,Antibodies, Viral ,Lymphocyte Activation ,medicine.disease_cause ,Asymptomatic ,Peripheral blood mononuclear cell ,Herpesviridae ,Virus ,Viral Envelope Proteins ,Virology ,medicine ,Humans ,Aged ,Herpes Genitalis ,biology ,Middle Aged ,Herpes simplex virus ,Immunology ,biology.protein ,Cytokines ,Female ,Viral disease ,medicine.symptom ,Antibody - Abstract
T-cell recognition of the secreted and membrane-bound portions of the herpes simplex virus type 2 (HSV-2) glycoprotein G (sgG-2 and mgG-2, respectively) was compared in symptomatic and asymptomatic HSV-2-infected individuals and in HSV-2-seronegative controls and the responses with HSV-1 glycoproteins C and E (gC-1 and gE-1) were compared. CD4+T cells from HSV-2-infected individuals specifically recognized both sgG-2 and mgG-2, whereas HSV-1-infected and HSV-seronegative controls did not respond to these glycoproteins. The responses to gC-1 and gE-1, on the other hand, were not type specific, as blood mononuclear cells from both HSV-1- and HSV-2-infected individuals respondedin vitro. There was an association between the status of the infection (symptomatic versus asymptomatic) and the CD4+T-cell responsiveness. Symptomatic HSV-2-seropositive individuals responded with significantly lower Th1 cytokine production to sgG-2 and mgG-2 than did asymptomatic HSV-2-infected carriers, especially within the HSV-1-negative cohort. No differences in T-cell proliferation were observed between asymptomatic and symptomatic individuals. The results have implications for studies of HSV-2-specific CD4+T-cell reactivity in general and for analysis of immunological differences between asymptomatic and symptomatic individuals in particular.
- Published
- 2004
32. Glycosaminoglycan-Binding Ability Is a Feature of Wild-Type Strains of Herpes Simplex Virus Type 1
- Author
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Maria E. Johansson, Tomas Bergström, Anette Roth, Edward Trybala, Elham Rekabdar, Olle Larm, and Jan-Åke Liljeqvist
- Subjects
viruses ,Molecular Sequence Data ,Herpesvirus 1, Human ,Biology ,medicine.disease_cause ,Virus ,chemistry.chemical_compound ,Mice ,L Cells ,Viral Envelope Proteins ,Virology ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,Chondroitin sulfate ,Vero Cells ,Glycosaminoglycans ,Glycosaminoglycan binding ,Nucleic acid sequence ,Wild type ,Herpes Simplex ,Heparan sulfate ,Sequence Analysis, DNA ,Molecular biology ,Adaptation, Physiological ,Herpes simplex virus ,chemistry ,Cell culture ,Heparitin Sulfate - Abstract
Adaptation of some viruses to replication in cultured cells selects variants that due to alterations in the viral attachment proteins convert to using heparan sulfate (HS) as initial receptor. We report that the nucleotide sequence of herpes simplex virus type 1 (HSV-1) glycoprotein C (gC), a principal attachment component of the virus, remained unchanged during adaptation of wild-type strains to cultured cells. Likewise, amino acid residues critical for binding of gC to HS were conserved in viral strains that replicated in vivo in different human tissues. Moreover wild-type HSV-1 strains derived directly from clinical specimens were, similar to their cell culture propagated progeny viruses and common laboratory strains, sensitive to heparin and demonstrated impairment in their ability to infect HS/chondroitin sulfate deficient cells. These results demonstrate that the HS-binding ability is a feature of wild-type strains of HSV-1.
- Published
- 2002
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33. Monoclonal antibodies and human sera directed to the secreted glycoprotein G of herpes simplex virus type 2 recognize type-specific antigenic determinants
- Author
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Jan-Åke Liljeqvist, Edward Trybala, Bo Svennerholm, Tomas Bergström, and Johan Hoebeke
- Subjects
medicine.drug_class ,Herpesvirus 2, Human ,Molecular Sequence Data ,Peptide ,Biology ,Antibodies, Viral ,Monoclonal antibody ,medicine.disease_cause ,Epitope ,Cell Line ,Mice ,Viral Envelope Proteins ,Antigen ,Antibody Specificity ,Virology ,Chlorocebus aethiops ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Antigens, Viral ,Mathematical Computing ,chemistry.chemical_classification ,Mice, Inbred BALB C ,medicine.diagnostic_test ,Antibodies, Monoclonal ,Molecular biology ,Herpes simplex virus ,chemistry ,Pepscan ,Immunoassay ,Epitopes, B-Lymphocyte ,Female ,Glycoprotein ,Epitope Mapping - Abstract
Glycoprotein G-2 (gG-2) of herpes simplex virus type 2 (HSV-2) is cleaved to a secreted amino-terminal portion (sgG-2) and to a cell-associated carboxy-terminal portion which is further O-glycosylated to constitute the mature gG-2 (mgG-2). In contrast to mgG-2, which is known to elicit a type-specific antibody response in the human host, information on the immunogenic properties of sgG-2 is lacking. Here the sgG-2 protein was purified on a heparin column and used for production of monoclonal antibodies (mAbs). Four anti-sgG-2 mAbs were mapped using a Pepscan technique and identified linear epitopes which localized to the carboxy-terminal part of the protein. One additional anti-sgG-2 mAb, recognizing a non-linear epitope, was reactive to three discrete peptide stretches where the most carboxy-terminally located stretch was constituted by the amino acids 320RRAL323. Although sgG-2 is rapidly secreted into the cell-culture medium after infection, the anti-sgG-2 mAbs identified substantial amounts of sgG-2 in the cytoplasm of HSV-2-infected cells. All of the anti-sgG-2 mAbs were HSV-2 specific showing no cross-reactivity to HSV-1 antigen or to HSV-1-infected cells. Similarly, sera from 50 HSV-2 isolation positive patients were all reactive to sgG-2 in an enzyme immunoassay whilst no reactivity was seen in 25 sera from HSV-1 isolation positive patients or in 25 serum samples from HSV-negative patients suggesting that sgG-2 is a novel antigen potentially suitable for type-discriminating serodiagnosis.
- Published
- 2002
34. Novel rat models to study primary genital herpes simplex virus-2 infection
- Author
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Karin Önnheim, Staffan Görander, Jan-Åke Liljeqvist, Eva Jennische, Tomas Bergström, Stefan Lange, Maria Ekblad, and Sheryl Wildt
- Subjects
medicine.medical_specialty ,viruses ,Herpesvirus 2, Human ,Inflammation ,Herpesvirus 1, Human ,Antibodies, Viral ,Asymptomatic ,Virus ,Medical microbiology ,Virology ,medicine ,Animals ,Herpes Genitalis ,biology ,General Medicine ,Spinal cord ,Survival Analysis ,Rats ,Microbicides for sexually transmitted diseases ,Disease Models, Animal ,medicine.anatomical_structure ,Immunology ,Vagina ,biology.protein ,Female ,Antibody ,Cortisone ,medicine.symptom ,medicine.drug - Abstract
In this study we describe that six rat models (SD, WIST, LEW, BN, F344 and DA) are susceptible to intravaginal herpes simplex virus-2 (HSV-2) infection after pre-treatment with progesterone. At a virus dose of 5 × 10(6) PFU of HSV-2, all rat models were infected presenting anti-HSV-2 antibodies, infectious virus in vaginal washes, and HSV-2 DNA genome copies in lumbosacral dorsal root ganglia and the spinal cord. Most of the LEW, BN, F344, and DA rats succumbed in systemic progressive symptoms at day 8-14 post infection, but presented no or mild genital inflammation while SD and WIST rats were mostly infected asymptomatically. Infected SD rats did not reactivate HSV-2 spontaneously or after cortisone treatment. In an HSV-2 virus dose reduction study, F344 rats were shown to be most susceptible. We also investigated whether an attenuated HSV-1 strain (KOS321) given intravaginally, could protect from a subsequent HSV-2 infection. All LEW, BN, and F344 rats survived a primary HSV-1 infection and no neuronal infection was established. In BN and F344 rats, anti-HSV-1 antibodies were readily detected while LEW rats were seronegative. In contrast to naïve LEW, BN, and F344 rats where only 3 of 18 animals survived 5 × 10(6) PFU of HSV-2, 23 of 25 previously HSV-1 infected rats survived a challenge with HSV-2. The described models provide a new approach to investigate protective effects of anti-viral microbicides and vaccine candidates, as well as to study asymptomatic primary genital HSV-2 infection.
- Published
- 2014
35. Rad51 and Rad52 are involved in homologous recombination of replicating herpes simplex virus DNA
- Author
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Peter Norberg, Ka-Wei Tang, Jan-Åke Liljeqvist, Per Elias, and Martin Holmudden
- Subjects
DNA Replication ,Viral Diseases ,DNA repair ,DNA recombination ,genetic processes ,RAD51 ,Sexually Transmitted Diseases ,lcsh:Medicine ,Genome, Viral ,Herpesvirus 1, Human ,Biology ,medicine.disease_cause ,Biochemistry ,Microbiology ,Cell Line ,Nucleic Acids ,Virology ,Molecular Cell Biology ,Recombinase ,medicine ,Medicine and Health Sciences ,Animals ,Humans ,RNA, Small Interfering ,lcsh:Science ,Homologous Recombination ,Multidisciplinary ,Biology and life sciences ,lcsh:R ,DNA replication ,Wild type ,Viral Replication Complex ,Herpes Simplex ,DNA ,Cell Biology ,Molecular biology ,Viral Replication ,Rad52 DNA Repair and Recombination Protein ,Herpes simplex virus ,Infectious Diseases ,Viral replication ,DNA, Viral ,lcsh:Q ,RNA Interference ,Rad51 Recombinase ,Homologous recombination ,Research Article - Abstract
Replication of herpes simplex virus 1 is coupled to recombination, but the molecular mechanisms underlying this process are poorly characterized. The role of Rad51 and Rad52 recombinases in viral recombination was examined in human fibroblast cells 1BR.3.N (wild type) and in GM16097 with replication defects caused by mutations in DNA ligase I. Intermolecular recombination between viruses, tsS and tsK, harboring genetic markers gave rise to ∼17% recombinants in both cell lines. Knock-down of Rad51 and Rad52 by siRNA reduced production of recombinants to 11% and 5%, respectively, in wild type cells and to 3% and 5%, respectively, in GM16097 cells. The results indicate a specific role for Rad51 and Rad52 in recombination of replicating herpes simplex virus 1 DNA. Mixed infections using clinical isolates with restriction enzyme polymorphisms in the US4 and US7 genes revealed recombination frequencies of 0.7%/kbp in wild type cells and 4%/kbp in GM16097 cells. Finally, tandem repeats in the US7 gene remained stable upon serial passage, indicating a high fidelity of recombination in infected cells.
- Published
- 2014
36. Conservation of Type-Specific B-Cell Epitopes of Glycoprotein G in Clinical Herpes Simplex Virus Type 2 Isolates
- Author
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Tomas Bergström, Jan-Åke Liljeqvist, and Bo Svennerholm
- Subjects
Microbiology (medical) ,Mutation ,Herpesvirus 2, Human ,Point mutation ,Molecular Sequence Data ,Antibodies, Monoclonal ,Biology ,medicine.disease_cause ,Virology ,Epitope ,Virus ,Herpes simplex virus ,Viral Envelope Proteins ,Antigen ,medicine ,Antigenic variation ,Epitopes, B-Lymphocyte ,Humans ,Point Mutation ,Amino Acid Sequence ,Peptide sequence - Abstract
Glycoprotein G (gG-2) of herpes simplex virus type 2 (HSV-2) is cleaved to a secreted amino-terminal portion and to a cell-associated, heavily O-glycosylated carboxy-terminal portion that constitutes the mature gG-2 (mgG-2). The mgG-2 protein is commonly used as a type-specific antigen in the serodiagnosis of HSV-2 infection. As the amino acid sequence variability of mgG-2 in clinical isolates may affect the performance of such assays, the gG-2 gene was sequenced from 15 clinical HSV-2 isolates. Few mutations were identified, and these were mostly localized outside the epitope regions described earlier. Five isolates were identical to different laboratory strains, indicating that the gG-2 gene is highly conserved over time. In the search for HSV-2 isolates harboring mutations within the immunodominant region of mgG-2, a pool of 2,400 clinical HSV-2 isolates was tested for reactivity with two anti-mgG-2 monoclonal antibodies (MAbs). Ten MAb escape HSV-2 mutants, which all harbored structurally restricted single- or dual-point mutations within the respective epitopes explaining the loss of binding, were identified. Sera from corresponding patients were reactive to mgG-2, as well as to a peptide representing the immunodominant region, suggesting that the point mutations detected did not diminish seroreactivity to mgG-2. The conservation of the gG-2 gene reported here further supports the use of mgG-2 as a type-specific antigen in the diagnosis of HSV-2 infections.
- Published
- 2000
37. Herpes Simplex Virus Types 1 and 2 Differ in Their Interaction with Heparan Sulfate
- Author
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Tomas Bergström, Jan-Åke Liljeqvist, Bo Svennerholm, and Edward Trybala
- Subjects
Herpesvirus 2, Human ,viruses ,Immunology ,Mutant ,Herpesvirus 1, Human ,Biology ,medicine.disease_cause ,Microbiology ,Virus ,chemistry.chemical_compound ,Viral Envelope Proteins ,Viral envelope ,Virology ,medicine ,Humans ,Receptor ,Glycoproteins ,chemistry.chemical_classification ,Genetic Variation ,Heparan sulfate ,Virus-Cell Interactions ,Herpes simplex virus ,Biochemistry ,chemistry ,Ionic strength ,Insect Science ,Heparitin Sulfate ,Glycoprotein - Abstract
Cell surface heparan sulfate (HS) serves as an initial receptor for many different viruses, including herpes simplex virus types 1 and 2 (HSV-1 and 2, respectively). Glycoproteins C and B (gC and gB) are the major components of the viral envelope that mediate binding to HS. In this study, purified gB and gC homologous proteins as well as purified HSV-1 and HSV-2 virions were compared for the ability to bind isolated HS receptor molecules. HSV-1 gC and HSV-2 gC bound comparable amounts of HS. Similarly, HSV-1 gB and its HSV-2 counterpart showed no difference in the HS-binding capabilities. Despite the similar HS-binding potentials of gB and gC homologs, HSV-1 virions bound more HS than HSV-2 particles. Purified gC and gB proteins differed with respect to sensitivity of their interaction with HS to increased concentrations of sodium chloride in the order gB-2 > gB-1 > gC-1 > gC-2. The corresponding pattern for binding of whole HSV virions to cells in the presence of increased ionic strength of the medium was HSV-2 gC-neg1 > HSV-1 gC − 39 > HSV-1 KOS 321 > HSV-2 333. These results relate the HS-binding activities of individual glycoproteins with the cell-binding abilities of whole virus particles. In addition, these data suggest a greater contribution of electrostatic forces for binding of gB proteins and gC-negative mutants compared with binding of gC homologs and wild-type HSV strains. Binding of wild-type HSV-2 virions was the least sensitive to increased ionic strength of the medium, suggesting that the less extensive binding of HS molecules by HSV-2 than by HSV-1 can be compensated for by a relatively weak contribution of electrostatic forces to the binding. Furthermore, gB and gC homologs exhibited different patterns of sensitivity of binding to cells to inhibition with selectively N-, 2-O-, and 6-O-desulfated heparin compounds. The O-sulfate groups of heparin were found to be more important for interaction with gB-1 than gB-2. These results indicate that HSV-1 and HSV-2 differ in their interaction with HS.
- Published
- 2000
38. Glycoprotein G of herpes simplex virus type 1: identification of type-specific epitopes by human antibodies
- Author
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Petra Tunbäck, Gun-Britt Löwhagen, Jan-Åke Liljeqvist, and Tomas Bergström
- Subjects
Molecular Sequence Data ,Herpesvirus 1, Human ,Biology ,medicine.disease_cause ,Antibodies ,Epitope ,Serology ,Epitopes ,Viral Envelope Proteins ,Antigen ,Antibody Specificity ,Virology ,medicine ,Humans ,Amino Acid Sequence ,Antigens, Viral ,Peptide sequence ,chemistry.chemical_classification ,Molecular biology ,Herpes simplex virus ,Epitope mapping ,chemistry ,biology.protein ,Antibody ,Glycoprotein ,Sequence Alignment ,Epitope Mapping - Abstract
Serological diagnosis of herpes simplex virus (HSV) infections requires assays based on antigens that expose type-specific determinants. This study was designed to outline the B-cell epitopes of the type-specific glycoprotein G-1 (gG-1) of HSV type 1 (HSV-1), by investigating the reactivity of human anti-gG-1 antibodies, purified from 21 HSV-1-isolation-proven patient sera, to cellulose-bound synthetic peptides spanning the entire gG-1 sequence. The epitope mapping demonstrated that these antibodies bound preferentially to antigenic determinants that localized to regions with a high degree of amino acid similarity to the corresponding glycoprotein in HSV-2, gG-2. In spite of this, the purified anti-gG-1 antibodies were found to be non-reactive to native gG-2 antigen, as well as to overlapping gG-2 peptides, thus supporting the role of gG-1 as a prototype HSV-1 type-specific antigen. One immunodominant region, delimited by amino acids 112-127, reacted with all purified anti-gG-1 antibodies and may be of interest for the further development of a peptide-based HSV-1 type-specific seroassay.
- Published
- 2000
39. Variability of the Glycoprotein G Gene in Clinical Isolates of Herpes Simplex Virus Type 1
- Author
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Petra Tunbäck, Jan-Åke Liljeqvist, Elham Rekabdar, and Tomas Bergström
- Subjects
Adult ,Male ,Microbiology (medical) ,Silent mutation ,DNA Mutational Analysis ,Molecular Sequence Data ,Clinical Biochemistry ,Immunology ,Enzyme-Linked Immunosorbent Assay ,Herpesvirus 1, Human ,Antibodies, Viral ,Kidney ,medicine.disease_cause ,Polymerase Chain Reaction ,Sensitivity and Specificity ,Article ,Epitope ,Epitopes ,Viral Envelope Proteins ,Chlorocebus aethiops ,Genetic variation ,medicine ,Animals ,Humans ,Immunology and Allergy ,Missense mutation ,Serologic Tests ,Amino Acid Sequence ,Gene ,Cells, Cultured ,Aged ,Mutation ,biology ,Antibodies, Monoclonal ,Genetic Variation ,Herpes Simplex ,Middle Aged ,Virology ,Molecular biology ,Herpes simplex virus ,Amino Acid Substitution ,Immunoglobulin G ,Antigens, Surface ,DNA, Viral ,biology.protein ,Female ,Antibody - Abstract
Glycoprotein G (gG) of herpes simplex virus type 1 (HSV-1) has been used as a prototype antigen for HSV-1 type-specific serodiagnosis, but data on the sequence variability of the gene coding for this protein in wild-type strains are lacking. In this study, direct DNA sequencing of the gG-1 genes from PCR products was performed with clinical HSV-1 isolates from 11 subjects as well as with strains Syn 17 + , F, and KOS 321. The reference strains Syn 17 + and F showed a high degree of conservation, while KOS 321 carried 13 missense mutations and, in addition, 12 silent mutations. Three clinical isolates showed mutations leading to amino acid alterations: one had a mutation of K 122 to N, which is a gG-1–to–gG-2 alteration; another contained all mutations which were observed in KOS 321 except two silent mutations; and the third isolate carried five missense mutations. Two clinical isolates as well as strain KOS 321 showed a mutation (F 111 →V) within the epitope of a gG-1-reactive monoclonal antibody (MAb). When all viruses were tested for reactivity with the anti-gG-1 MAb, the three strains with the F 111 →V mutation were found to be unreactive. Furthermore, gG-1 antibodies purified from sera from the two patients carrying strains mutated in this epitope were less reactive when they were tested by an HSV-1-infected-cell assay. Therefore, our finding that the sequence variability of the gG-1 gene also affects B-cell epitope regions of this protein in clinical isolates may have consequences for the use of this protein as a type-specific antigen for serodiagnosis.
- Published
- 1999
40. A genome-wide comparative evolutionary analysis of herpes simplex virus type 1 and varicella zoster virus
- Author
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Tomas Bergström, Shaun Tyler, Peter Norberg, Jan-Åke Liljeqvist, Alberto Severini, and Rich Whitley
- Subjects
Viral Diseases ,Herpesvirus 3, Human ,Genome evolution ,Evolutionary Processes ,Time Factors ,viruses ,Mucocutaneous zone ,lcsh:Medicine ,Parallel Evolution ,Genome, Viral ,Herpesvirus 1, Human ,Biology ,Forms of Evolution ,medicine.disease_cause ,Genome ,Shingles ,Evolution, Molecular ,Chickenpox ,Phylogenetics ,medicine ,Humans ,Evolutionary Systematics ,lcsh:Science ,Phylogeny ,Recombination, Genetic ,Genetics ,Evolutionary Biology ,Multidisciplinary ,integumentary system ,Human evolutionary genetics ,lcsh:R ,Varicella zoster virus ,Genetic Variation ,virus diseases ,Herpes Simplex ,Genomics ,Virology ,Organismal Evolution ,Infectious Diseases ,Herpes simplex virus ,Viral evolution ,Mutation ,Microbial Evolution ,Medicine ,lcsh:Q ,Research Article ,Coevolution - Abstract
Herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) are closely related viruses causing lifelong infections. They are typically associated with mucocutaneous or skin lesions, but may also cause severe neurological or ophthalmic diseases, possibly due to viral- and/or host-genetic factors. Although these viruses are well characterized, genome-wide evolutionary studies have hitherto only been presented for VZV. Here, we present a genome-wide study on HSV-1. We also compared the evolutionary characteristics of HSV-1 with those for VZV. We demonstrate that, in contrast to VZV for which only a few ancient recombination events have been suggested, all HSV-1 genomes contain mosaic patterns of segments with different evolutionary origins. Thus, recombination seems to occur extremely frequent for HSV-1. We conclude by proposing a timescale for HSV-1 evolution, and by discussing putative underlying mechanisms for why these otherwise biologically similar viruses have such striking evolutionary differences.
- Published
- 2011
41. Failure to demonstrate enterovirus aetiology in Swedish patients with dilated cardiomyopathy
- Author
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G.E. Yousef, Finn Waagstein, Tomas Bergström, Stefan Holmström, Jan-Åke Liljeqvist, Stig Jeansson, and Agneta Samuelson
- Subjects
Cardiomyopathy, Dilated ,Molecular Sequence Data ,Cardiomyopathy ,Enzyme-Linked Immunosorbent Assay ,medicine.disease_cause ,Polymerase Chain Reaction ,Sensitivity and Specificity ,Virus ,Serology ,Feces ,Virology ,Enterovirus Infections ,medicine ,Humans ,Antigens, Viral ,Enterovirus ,Base Sequence ,biology ,medicine.diagnostic_test ,Incidence ,Dilated cardiomyopathy ,medicine.disease ,Enterovirus B, Human ,Infectious Diseases ,Immunoglobulin M ,Immunoglobulin G ,Immunoassay ,Immunology ,biology.protein ,RNA, Viral ,Viral disease ,Antibody - Abstract
Attempts were made to establish a possible relationship between enterovirus infection and dilated cardiomyopathy (DCM) by use of serology, virus isolation from faecal samples, and detection of enteroviral RNA in endomyocardial biopsies (EMB) by the polymerase chain reaction (PCR). Sera from 63 patients with DCM and matched controls were examined for enterovirus infection by p.-capture IgM and indirect IgG ELISA. Thirty-six patients were further tested for the presence of enterovirus group-specific antigen (VPI) in an immunoassay system. The results were consistently negative. Faecal samples from 35 of these patients were negative by enterovirus isolation both when samples were cultured directly and after acid treatment. EMB from 35 patients were examined for enteroviral RNA by PCR; none of the samples was reactive. In conclusion, the results fail to indicate involvement of enteroviruses in the aetiology of DCM. (0 1993 Wiley-Liss, Inc.
- Published
- 1993
42. Risk factors for death and mode of death after acute myocardial infarction in relation to age
- Author
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Björn W. Karlson, Åke Hjalmarson, Per Pettersson, Jan-Åke Liljeqvist, Johan Herlitz, and Ulf Strömbom
- Subjects
medicine.medical_specialty ,business.industry ,Infarction ,General Medicine ,medicine.disease ,Risk indicators ,Age groups ,Internal medicine ,medicine ,In patient ,Myocardial infarction ,Cardiology and Cardiovascular Medicine ,Intensive care medicine ,business - Abstract
Background: This study aims to describe independent risk indicators for death and mode of death after development of acute myocardial infarction in relation to age. Methods: Nine hundred twenty-one consecutive patients admitted to Sahlgrenska Hospital, Goteborg, Sweden, suffering from acute myocardial infarction were prospectively followed for 1 year. The patients were divided into two age groups, 76 years old and above or below 76 years old, because there was an equal number of deaths in these two groups. Results: In the older group, the following were independent risk indicators for death at 1 year of follow-up, in order of significance: 1) previous infarction (P 76 y) with acute myocardial infarction, risk indicators for death differ from those in younger patients. Symptoms associated with death are also not the same in patients 76 years old as compared with younger patients.
- Published
- 1992
43. Early identification of acute myocardial infarction and prognosis in relation to mode of transport to hospital
- Author
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Jan-Åke Liljeqvist, Björn W. Karlson, Stig Holmberg, Johan Herlitz, and Ulf Strömbom
- Subjects
Male ,Chest Pain ,Emergency Medical Services ,medicine.medical_specialty ,Myocardial Infarction ,Early death ,Hospitals, University ,medicine ,Humans ,Thrombolytic Therapy ,In patient ,cardiovascular diseases ,Myocardial infarction ,Intensive care medicine ,Aged ,Sweden ,business.industry ,General Medicine ,Emergency department ,Middle Aged ,Prognosis ,University hospital ,medicine.disease ,Prehospital thrombolysis ,Transportation of Patients ,Emergency medicine ,Emergency Medicine ,Coronary care unit ,Female ,Emergency Service, Hospital ,business ,Mobile Health Units ,Delay time - Abstract
Of 2,840 consecutive patients who were admitted to the emergency department of a Swedish university hospital due to suspected acute myocardial infarction (AMI), only 25% were reached by the mobile coronary care unit (MCCU), and only 4% simultaneously fulfilled traditional criteria for prehospital thrombolysis (ie, had ST-segment elevation on admission electrocardiogram and a delay time of less than 6 hours). In the subset of patients who fulfilled criteria for a confirmed AMI, 31% were reached by an MCCU and 11% fulfilled criteria for prehospital thrombolysis. Among patients with confirmed AMI, the hospital mortality rate was highest in patients transported by standard ambulance (19%) versus 15% in those transported by an MCCU and 8% in those transported by other means. The authors conclude that AMI patients transported by ambulance are high-risk patients for early death. Prehospital thrombolysis might reduce their rate of mortality. However, according to the authors' experience only a minor fraction of patients are available for prehospital thrombolysis.
- Published
- 1992
44. Characterization of polyclonal antibodies against the capsid proteins of Ljungan virus
- Author
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Bo Niklasson, Kjell Edman, A. Michael Lindberg, Conny Tolf, Jan-Åke Liljeqvist, Gustav Arbrandt, Maria Gullberg, Gun Frisk, and Jens-Ola Ekström
- Subjects
viruses ,Blotting, Western ,Parechovirus ,Enzyme-Linked Immunosorbent Assay ,Cross Reactions ,Immunofluorescence ,Antibodies, Viral ,Monocytes ,law.invention ,Mice ,law ,Virology ,medicine ,Animals ,Fluorescent Antibody Technique, Indirect ,Picornaviridae Infections ,medicine.diagnostic_test ,biology ,Human parechovirus ,Virion ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Ljungan virus ,Capsid ,Polyclonal antibodies ,biology.protein ,Recombinant DNA ,Capsid Proteins ,Antibody - Abstract
Ljungan virus (LV) is a suspected human pathogen isolated from voles in Sweden and North America. To enable virus detection and studies of localization and activity of virion proteins, polyclonal antibodies were produced against bacterially expressed capsid proteins of the LV strain, 87-012G. Specific detection of proteins corresponding to viral antigens in lysates of LV infected cells was demonstrated by immunoblotting using each one of the generated polyclonal antibodies. In addition, native viral antigens present in cell culture infected with LV strains 87-012G or 145SLG were detected in ELISA and by immunofluorescence using the antibodies against the VP0 and VP1 proteins. The anti-VP3 antibody did not react with native proteins of the LV virion, suggesting that the VP3 is less potent in evoking humoral response and may have a less exposed orientation in the virus capsid. No activity of the antibodies was observed against the closely related human parechovirus type 1. The polyclonal antibody against the VP1 protein was further used for detection of LV infected myocytes in a mouse model of LV-induced myocarditis. Thus, polyclonal antibodies against recombinant viral capsid proteins enabled detection of natural LV virions by several different immunological methods.
- Published
- 2007
45. Divergence and recombination of clinical herpes simplex virus type 2 isolates
- Author
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Tomas Bergström, Lars Haarr, Peter Norberg, Jan-Åke Liljeqvist, and Mabula Kasubi
- Subjects
Nonsynonymous substitution ,Genotype ,Sequence analysis ,viruses ,Herpesvirus 2, Human ,Immunology ,Molecular Sequence Data ,Biology ,medicine.disease_cause ,Microbiology ,Tanzania ,Virus ,Evolution, Molecular ,Viral Envelope Proteins ,Phylogenetics ,Virology ,medicine ,Cluster Analysis ,Humans ,Genetic variability ,Gene ,Phylogeny ,Genetics ,Recombination, Genetic ,Sweden ,Herpes Genitalis ,Polymorphism, Genetic ,Phylogenetic tree ,Geography ,Sequence Homology, Amino Acid ,Norway ,Sequence Analysis, DNA ,Herpes simplex virus ,Genetic Diversity and Evolution ,Insect Science ,DNA, Viral - Abstract
Herpes simplex virus type 2 (HSV-2) infects the genital mucosa and is one of the most common sexually transmitted viruses. Here we sequenced a segment comprising 3.5% of the HSV-2 genome, including genes coding for glycoproteins G, I, and E, from 27 clinical isolates from Tanzania, 10 isolates from Norway, and 10 isolates from Sweden. The sequence variation was low compared to that described for clinical HSV-1 isolates, with an overall similarity of 99.6% between the two most distant HSV-2 isolates. Phylogenetic analysis revealed a divergence into at least two genogroups arbitrarily designated A and B, supported by high bootstrap values and evolutionarily separated at the root. Genogroup A contained isolates collected in Tanzania, and genogroup B contained isolates collected in Tanzania and Scandinavia, implying that the genetic variability of HSV-2 is higher in Tanzania than in Scandinavia. Recombination network analysis and bootscan analysis revealed a complex pattern of phylogenetically conflicting informative sites in the sequence alignments. These signals were present in synonymous and nonsynonymous sites in all three genes and were not accumulated in specific regions, observations arguing against positive selection. Since the PHI test applied solely to synonymous sites revealed a high statistical probability of recombination, we suggest as a novel finding that homologous recombination is, as reported earlier for HSV-1 and varicella-zoster virus, a prominent feature in the evolution of HSV-2.
- Published
- 2007
46. Complete-Genome Phylogenetic Approach to Varicella-Zoster Virus Evolution: Genetic Divergence and Evidence for Recombination
- Author
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D. Scott Schmid, Peter Norberg, Jan-Åke Liljeqvist, Scott Sammons, Tomas Bergström, and Vladimir N. Loparev
- Subjects
Genetics ,Recombination, Genetic ,Herpesvirus 3, Human ,Phylogenetic tree ,Base Sequence ,viruses ,Immunology ,Varicella zoster virus ,Genome, Viral ,Biology ,medicine.disease_cause ,Microbiology ,Genome ,Virus ,Tandem repeat ,Genetic Diversity and Evolution ,Phylogenetics ,Virology ,Insect Science ,GenBank ,medicine ,Genotyping ,Phylogeny - Abstract
Recent studies of varicella-zoster virus (VZV) DNA sequence variation, involving large numbers of globally distributed clinical isolates, suggest that this virus has diverged into at least three distinct genotypes designated European (E), Japanese (J), and mosaic (M). In the present study, we determined and analyzed the complete genomic sequences of two M VZV strains and compared them to the sequences of three E strains and two J strains retrieved from GenBank (including the Oka vaccine preparation, V-Oka). Except for a few polymorphic tandem repeat regions, the whole genome, representing approximately 125,000 nucleotides, is highly conserved, presenting a genetic similarity between the E and J genotypes of approximately 99.85%. These analyses revealed that VZV strains distinctly segregate into at least four genotypes (E, J, M1, and M2) in phylogenetic trees supported by high bootstrap values. Separate analyses of informative sites revealed that the tree topology was dependent on the region of the VZV genome used to determine the phylogeny; collectively, these results indicate the observed strain variation is likely to have resulted, at least in part, from interstrain recombination. Recombination analyses suggest that strains belonging to the M1 and M2 genotypes are mosaic recombinant strains that originated from ancestral isolates belonging to the E and J genotypes through recombination on multiple occasions. Furthermore, evidence of more recent recombination events between M1 and M2 strains is present in six segments of the VZV genome. As such, interstrain recombination in dually infected cells seems to figure prominently in the evolutionary history of VZV, a feature it has in common with other herpesviruses. In addition, we report here six novel genomic targets located in open reading frames 51 to 58 suitable for genotyping of clinical VZV isolates.
- Published
- 2006
47. Characterization of T-cell reactive epitopes in glycoprotein G of herpes simplex virus type 2 using synthetic peptides
- Author
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Petra Tunbäck, Kristina Eriksson, G.-B. Löwhagen, Jan-Åke Liljeqvist, Inger Nordström, and Lars Bellner
- Subjects
chemistry.chemical_classification ,Adult ,CD4-Positive T-Lymphocytes ,Male ,Herpesvirus 2, Human ,General Medicine ,Biology ,medicine.disease_cause ,Antibodies, Viral ,Herpesvirus glycoprotein B ,Virology ,Herpesviridae ,Virus ,Epitope ,Amino acid ,Epitopes ,Herpes simplex virus ,chemistry ,Viral Envelope Proteins ,medicine ,Humans ,Female ,Glycoprotein ,Peptide sequence - Abstract
We have previously shown that the CD4+ T-cell response to herpes simplex virus type 2 glycoprotein G-2 is type-specific and can thus be used to evaluate herpes simplex virus type 2-specific T-cell responses in individuals with a concomitant herpes simplex virus type 1 infection. In this study we have followed the glycoprotein G-2-specific T-cell responses over time, and also tried to identify T-cell epitopes in the membrane bound portion and the secreted portion of glycoprotein G-2 using synthetic peptides spanning the whole amino acid sequence of glycoprotein G-2. We found that the magnitude of the glycoprotein G-2-specific response varied considerably in infected individuals over time, even though all patients responded to at least one of the two glycoproteins at all time-points examined. We could also document strong T-cell responses to synthetic peptides from the secreted glycoprotein G-2 but only low responses to synthetic peptides corresponding to sequences from the heavily glycosylated membrane-bound glycoprotein G-2. We were able to map an immunogenic region (amino acid 31–125) within the secreted glycoprotein G-2. This region of the glycoprotein induced proliferative responses in 47% of the herpes simplex virus type 2-infected individuals. However, we were not able to identify any universal T-cell epitope.
- Published
- 2004
48. Phylogenetic Analysis of Clinical Herpes Simplex Virus Type 1 Isolates Identified Three Genetic Groups and Recombinant Viruses
- Author
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Magnus Lindh, Elham Rekabdar, Tomas Bergström, Peter Norberg, and Jan-Åke Liljeqvist
- Subjects
Male ,Genotype ,Sequence analysis ,Immunology ,Molecular Sequence Data ,Sequence Homology ,Herpesvirus 1, Human ,Biology ,medicine.disease_cause ,Microbiology ,Genome ,Frameshift mutation ,Intergenic region ,Tandem repeat ,Viral Envelope Proteins ,Virology ,medicine ,Humans ,Genitalia ,Frameshift Mutation ,Gene ,Phylogeny ,Genetics ,Recombination, Genetic ,Molecular Epidemiology ,Mouth ,Polymorphism, Genetic ,Base Sequence ,Herpes Simplex ,Sequence Analysis, DNA ,Herpes simplex virus ,Tandem Repeat Sequences ,Insect Science ,GenBank ,DNA, Viral ,Recombination and Evolution ,Encephalitis ,Female - Abstract
Herpes simplex virus type 1 (HSV-1) is a ubiquitous human pathogen which establishes lifelong infections. In the present study, we determined the sequence diversity of the complete genes coding for glycoproteins G (gG), I (gI), and E (gE), comprising 2.3% of the HSV-1 genome and located within the unique short (US) region, for 28 clinical HSV-1 isolates inducing oral lesions, genital lesions, or encephalitis. Laboratory strains F and KOS321 were sequenced in parallel. Phylogenetic analysis, including analysis of laboratory strain 17 (GenBank), revealed that the sequences were separated into three genetic groups. The identification of different genogroups facilitated the detection of recombinant viruses by using specific nucleotide substitutions as recombination markers. Seven of the isolates and strain 17 displayed sequences consistent with intergenic recombination, and at least four isolates were intragenic recombinants. The observed frequency of recombination based on an analysis of a short stretch of the US region suggests that most full-length HSV-1 genomes consist of a mosaic of segments from different genetic groups. Polymorphic tandem repeat regions, consisting of two to eight blocks of 21 nucleotides in the gI gene and seven to eight repeats of 3 nucleotides in the gG gene, were also detected. Laboratory strain KOS321 displayed a frameshift mutation in the gI gene with a subsequent alteration of the deduced intracellular portion of the protein. The presence of polymorphic tandem repeat regions and the different genogroup identities can be used for molecular epidemiology studies and for further detection of recombination in the HSV-1 genome.
- Published
- 2004
49. Secreted portion of glycoprotein g of herpes simplex virus type 2 is a novel antigen for type-discriminating serology
- Author
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Bo Svennerholm, Staffan Görander, and Jan-Åke Liljeqvist
- Subjects
Microbiology (medical) ,Herpesvirus 2, Human ,Cytomegalovirus ,Enzyme-Linked Immunosorbent Assay ,Herpesvirus 1, Human ,medicine.disease_cause ,Sensitivity and Specificity ,Immunoglobulin G ,Serology ,Antigen ,Viral Envelope Proteins ,Virology ,medicine ,Humans ,Seroconversion ,Serotyping ,First episode ,Blood Specimen Collection ,biology ,Reproducibility of Results ,Herpes Simplex ,Molecular biology ,Herpes simplex virus ,Immunoglobulin M ,biology.protein ,Antibody - Abstract
The secreted portion of glycoprotein G (sgG-2) of herpes simplex virus type 2 (HSV-2) was evaluated as a novel antigen in an enzyme-linked immunosorbent assay (ELISA) format for detection of type-specific immunoglobulin G (IgG) antibodies in HSV-2-infected patients. The results were compared with those obtained by a commercially available assay, the HerpeSelect 2 ELISA (the FOCUS2 assay). Five different panels of sera were analyzed: panel A consisted of 109 serum samples from patients with a culture-proven HSV-1 infection that were Western blotting (WB) negative for HSV-2; panel B consisted of 106 serum samples from patients with a culture-proven recurrent HSV-2 infection that were WB positive for HSV-2; panel C consisted of 100 serum samples with no detectable IgG antibodies against HSV-1 and HSV-2; panel D consisted of 70 HSV-2 negative “tricky” serum samples containing antinuclear IgG antibodies or IgM antibodies against other viruses or bacteria; and panel E consisted of consecutive serum samples from 21 patients presenting with a first episode of HSV-2-induced lesions. When sera in panels A to C were analyzed, the sgG-2 ELISA and the FOCUS2 assay both showed sensitivities and specificities of ≥98%. In total, among the samples in panel D, 13 serum samples (19%) were false positive by the FOCUS2 assay and 1 serum sample (1.4%) was false positive by the sgG-2 ELISA. When the sera in panel E were analyzed, the sgG-2 ELISA detected seroconversion somewhat later than WB or the FOCUS2 assay did. We conclude that sgG-2 induces an HSV-2 type-specific antibody response and can be used for type-discriminating serology.
- Published
- 2003
50. Dichotomy of Glycoprotein G Gene in Herpes Simplex Virus Type 1 Isolates
- Author
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Jan-Åke Liljeqvist, Elham Rekabdar, Petra Tunbäck, Tomas Bergström, and Magnus Lindh
- Subjects
Microbiology (medical) ,Molecular Sequence Data ,Enzyme-Linked Immunosorbent Assay ,Immunodominance ,Herpesvirus 1, Human ,Biology ,medicine.disease_cause ,Antibodies, Viral ,Epitope ,Virus ,Frameshift mutation ,Cell Line ,Cytosine nucleotide ,Viral Envelope Proteins ,Virology ,medicine ,Humans ,Amino Acid Sequence ,Frameshift Mutation ,Gene ,Immunodominant Epitopes ,Antibodies, Monoclonal ,Genetic Variation ,Herpes Simplex ,Sequence Analysis, DNA ,Molecular biology ,Herpes simplex virus ,biology.protein ,Antibody - Abstract
Herpes simplex virus type 1 (HSV-1) encodes 11 envelope glycoproteins, of which glycoprotein G-1 (gG-1) induces a type-specific antibody response. Variability of the gG-1 gene among wild-type strains may be a factor of importance for a reliable serodiagnosis and typing of HSV-1 isolates. Here, we used a gG-1 type-specific monoclonal antibody (MAb) to screen for mutations in the immunodominant region of this protein in 108 clinical HSV-1 isolates. Of these, 42 isolates showed no reactivity to the anti-gG-1 MAb. One hundred five strains were further examined by DNA sequencing of the middle part of the gG-1 gene, encompassing 106 amino acids including the immunodominant region and epitope of the anti-gG-1 MAb. By phylogenetic comparisons based on the sequence data, we observed two (main) genetic variants of the gG-1 gene among the clinical isolates corresponding to reactivity or nonreactivity to the anti-gG-1 MAb. Furthermore, four strains appeared to be recombinants of the two gG-1 variants. In addition, one strain displayed a gG-1-negative phenotype due to a frameshift mutation, in the form of insertion of a cytosine nucleotide. When immunoglobulin G reactivity to HSV-1 in sera from patients infected with either of the two variants was investigated, no significant differences were found between the two groups, either in a type-common enzyme-linked immunosorbent assay (ELISA) or in a type-specific gG-1 antigen-based ELISA. Despite the here-documented existence of two variants of the gG-1 gene affecting the immunodominant region of the protein, other circumstances, such as early phase of infection, might be sought for explaining the seronegativity to gG-1 commonly found in a proportion of the HSV-1-infected patients.
- Published
- 2002
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