762 results on '"Herpesvirus 6, Human"'
Search Results
2. Human Herpesvirus 6 Meningitis in a Neonatal Case
- Author
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Gyu Min Yeon and Yu Jin Jung
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herpesvirus 6, human ,meningitis ,infant, newborn ,Pediatrics ,RJ1-570 - Abstract
Incidence of human herpesvirus-6 (HHV-6) infection in the neonatal period has been reported in few cases. HHV-6, commonly responsible for roseola, is known to establish infection during infancy and early childhood. A 14-day-old neonate, presented with a fever of 38.3℃, primarily due to an HHV-6 infection, was admitted to our neonatal intensive care unit. A polymerase chain reaction (PCR) of his cerebrospinal fluid was positive for HHV-6. Additionally, serology for HHV-6 PCR was positive. We believe that HHV-6 can cause infection in febrile newborn infants.
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- 2021
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3. Association between human herpesvirus-6 encephalitis and antiviral prophylaxis after allogeneic hematopoietic stem cell transplantation in the letermovir era.
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Terao T, Matsuoka KI, Fuji S, Kawamura S, Toya T, Doki N, Uchida N, Tanaka M, Fukuda T, Sawa M, Ishikawa J, Nishida T, Ohigashi H, Maruyama Y, Fujiwara SI, Kanda Y, Ota S, Ishimaru F, Atsuta Y, Kanda J, Ogata M, Yakushijin K, and Nakasone H
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- Humans, Male, Adult, Female, Middle Aged, Quinazolines therapeutic use, Triazoles therapeutic use, Transplantation, Homologous, Acetates, Hematopoietic Stem Cell Transplantation adverse effects, Antiviral Agents therapeutic use, Encephalitis, Viral prevention & control, Encephalitis, Viral etiology, Roseolovirus Infections prevention & control, Roseolovirus Infections etiology, Herpesvirus 6, Human
- Abstract
The impact of letermovir (LTV)-an anti-cytomegalovirus (CMV) drug-on human herpesvirus-6 (HHV-6) encephalitis is unclear. We hypothesized that LTV prophylaxis may increase the incidence of HHV-6 encephalitis by reducing anti-CMV therapies after allogeneic hematopoietic stem cell transplantation (HSCT). To evaluate the association between HHV-6 encephalitis and antiviral prophylaxis, 7985 adult patients from a nationwide registry who underwent their first HSCT between January 2019 and December 2021 were analyzed. The incidence of HHV-6 encephalitis on day 100 after HSCT was 3.6%; 11.5% for the broad-spectrum antiviral group (foscarnet, ganciclovir, or valganciclovir); 2.8% for the LTV group, and 3.8% for the other antiviral group (p < 0.001). These differences persisted when cord blood transplantation (CBT) was analyzed separately (14.1%, 5.9%, and 7.4%, p < 0.001). In the multivariate analysis, CBT (hazard ratio [HR]: 2.90), broad-spectrum antiviral prophylaxis (HR: 1.91), and grade II-IV acute graft-versus-host disease requiring systemic corticosteroids (HR: 2.42) were independent risk factors for encephalitis (all p < 0.001). The findings of this large modern database study indicate that broad-spectrum antiviral prophylaxis, rather than LTV prophylaxis, is paradoxically associated with HHV-6 encephalitis in the LTV era. This paradoxical finding needs to be further explored in future studies., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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4. Additive effects of EBV and HHV-6A on MS risk.
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Wood H
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- Humans, Risk Factors, Herpesvirus 6, Human, Roseolovirus Infections complications, Epstein-Barr Virus Infections complications, Herpesvirus 4, Human, Multiple Sclerosis virology, Multiple Sclerosis epidemiology
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- 2024
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5. Human herpesvirus-6, HHV-8 and parvovirus B19 after allogeneic hematopoietic cell transplant: the lesser-known viral complications.
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Kampouri E, Little JS, Crocchiolo R, and Hill JA
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- Humans, Parvoviridae Infections epidemiology, Parvoviridae Infections diagnosis, Antiviral Agents therapeutic use, Roseolovirus Infections epidemiology, Roseolovirus Infections virology, Roseolovirus Infections diagnosis, Transplantation, Homologous adverse effects, Herpesviridae Infections epidemiology, Herpesviridae Infections virology, Hematopoietic Stem Cell Transplantation adverse effects, Herpesvirus 8, Human, Parvovirus B19, Human isolation & purification, Herpesvirus 6, Human
- Abstract
Purpose of Review: Viral infections continue to burden allogeneic hematopoietic cell transplant (HCT) recipients. We review the epidemiology, diagnosis, and management of human herpesvirus (HHV)-6, HHV-8 and parvovirus B19 following HCT., Recent Findings: Advances in HCT practices significantly improved outcomes but impact viral epidemiology: post-transplant cyclophosphamide for graft-versus-host disease prevention increases HHV-6 reactivation risk while the impact of letermovir for CMV prophylaxis - and resulting decrease in broad-spectrum antivirals - is more complex. Beyond the well established HHV-6 encephalitis, recent evidence implicates HHV-6 in pneumonitis. Novel less toxic therapeutic approaches (brincidofovir, virus-specific T-cells) may enable preventive strategies in the future. HHV-8 is the causal agent of Kaposi's sarcoma, which is only sporadically reported after HCT, but other manifestations are possible and not well elucidated. Parvovirus B19 can cause severe disease post-HCT, frequently manifesting with anemia, but can also be easily overlooked due to lack of routine screening and ambiguity of manifestations., Summary: Studies should establish the contemporary epidemiology of HHV-6, and other more insidious viruses, such as HHV-8 and parvovirus B19 following HCT and should encompass novel cellular therapies. Standardized and readily available diagnostic methods are key to elucidate epidemiology and optimize preventive and therapeutic strategies to mitigate the burden of infection., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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6. Bis-tridentate Iridium(III) Complex with the N-Heterocyclic Carbene Ligand as a Novel Efficient Electrochemiluminescence Emitter for the Sandwich Immunoassay of the HHV-6A Virus.
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Dai C, Mao Z, Xu Y, Jia J, Tang H, Zhao Y, and Zhou Y
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- Humans, Immunoassay methods, Ligands, Methane chemistry, Heterocyclic Compounds chemistry, Iridium chemistry, Herpesvirus 6, Human, Coordination Complexes chemistry, Luminescent Measurements methods, Electrochemical Techniques methods, Methane analogs & derivatives
- Abstract
Human herpesvirus type 6A (HHV-6A) can cause a series of immune and neurological diseases, and the establishment of a sensitive biosensor for the rapid detection of HHV-6A is of great significance for public health and safety. Herein, a bis-tridentate iridium complex (BisL
T -Ir-NHC) comprising the N-heterocyclic carbene (NHC) ligand as a novel kind of efficient ECL luminophore has been unprecedently reported. Based on its excellent ECL properties, a new sensitive ECL-based sandwich immunosensor to detect the HHV-6A virus was successfully constructed by encapsulating BisLT -Ir-NHC into silica nanoparticles and embellishing ECL sensing interface with MXene@Au-CS. Notably, the immunosensor illustrated in this work not only had a wide linear range of 102 to 107 cps/μL but also showed outstanding recoveries (98.33-105.11%) in real human serum with an RSD of 0.85-3.56%. Undoubtedly, these results demonstrated the significant potential of the bis-tridentate iridium(III) complex containing an NHC ligand in developing ECL-based sensitive analytical methods for virus detection and exploring novel kinds of efficient iridium-based ECL luminophores in the future.- Published
- 2024
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7. DRESS syndrome with multiorgan involvement and HHV-6 reactivation in the absence of a drug trigger.
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Aw YTV, Ooi M, and Ekladious A
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- Female, Humans, Middle Aged, Herpesvirus 6, Human, Drug Hypersensitivity Syndrome diagnosis, Myocarditis, Eosinophilia, Heart Failure
- Abstract
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug reaction where patients present with fever, morbilliform rash and multiorgan manifestations, which may include acute renal failure, acute respiratory distress syndrome and eosinophilic myocarditis. We present a case of a 60-year-old woman with acute heart failure, DRESS syndrome features and human herpesvirus 6 reactivation in the absence of a drug trigger. She was diagnosed with eosinophilic myocarditis and successfully treated with corticosteroid therapy., (© 2024 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)
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- 2024
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8. Viral etiology of measles-like rash in Guinean children during the COVID epidemic in 2022.
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Anguinze RS, Touré A, Cissé F, Grayo S, Troupin C, Tordo N, Kouamou E, and Roques P
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- Child, Humans, Infant, Child, Preschool, Papua New Guinea, Antibodies, Viral, Immunoglobulin M, Guinea, Measles virus genetics, COVID-19 epidemiology, COVID-19 complications, Measles, Rubella, Parvovirus B19, Human genetics, Exanthema, Herpesvirus 6, Human
- Abstract
Covid-19 in West Africa masked outbreaks of vaccine-preventable diseases such as the measles epidemic in children in Guinea in 2021-2022 characterized by a lack of confirmation of suspected clinical cases. During weeks 13-22 of 2022, saliva samples were collected from 213 children (3-60 months old) with measles-like symptoms within the St Gabriel dispensary in Conakry. Samples were processed in Virus Transport Medium (VTM) and tested on the same day by triplex reverse transcriptase -real-time polymerase chain reaction for Measles, Rubella and RNaseP. Samples were also tested for HHV6 and Parvovirus B19, viruses causing clinical signs similar to measles. We confirmed 146 (68.5%) measles cases, 27 (12.7%) rubella, 5 (2.3%) double-positive measles-rubella, 35 (16.4%) HHV-6 and 8 (3.75%) Parvovirus B19. To test the assay's robustness, 27 samples were kept at 26-30°C. Measles and rubella were still detected after 7 days at 26-30°C, and after 21 days measles and rubella were still detectable in all samples but one. Sequencing indicated the circulation of the B3 measles genotype, as expected in West Africa. This study highlights the robustness of the measles/rubella diagnostic test on saliva samples stored in VTM. The high level of rubella detection questioned the single valence measles vaccination strategy., (© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)
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- 2024
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9. Herpes viral infection and the multiple sclerosis prodrome: is HHV-6A infection a second hit?
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Cree BAC
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- Humans, Axons, Herpesvirus 6, Human, Multiple Sclerosis complications, Multiple Sclerosis virology, Virus Diseases
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- 2024
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10. Human herpesvirus 6A and axonal injury before the clinical onset of multiple sclerosis.
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Grut V, Biström M, Salzer J, Stridh P, Jons D, Gustafsson R, Fogdell-Hahn A, Huang J, Butt J, Lindam A, Alonso-Magdalena L, Bergström T, Kockum I, Waterboer T, Olsson T, Zetterberg H, Blennow K, Andersen O, Nilsson S, and Sundström P
- Subjects
- Humans, Antibodies, Biomarkers, Case-Control Studies, Herpesvirus 4, Human, Male, Female, Epstein-Barr Virus Infections, Herpesvirus 6, Human, Multiple Sclerosis
- Abstract
Recent research indicates that multiple sclerosis is preceded by a prodromal phase with elevated levels of serum neurofilament light chain (sNfL), a marker of axonal injury. The effect of environmental risk factors on the extent of axonal injury during this prodrome is unknown. Human herpesvirus 6A (HHV-6A) is associated with an increased risk of developing multiple sclerosis. The objective of this study was to determine if HHV-6A serostatus is associated with the level of sNfL in the multiple sclerosis prodrome, which would support a causative role of HHV-6A. A nested case-control study was performed by crosslinking multiple sclerosis registries with Swedish biobanks. Individuals with biobank samples collected before the clinical onset of multiple sclerosis were included as cases. Controls without multiple sclerosis were randomly selected, matched for biobank, sex, sampling date and age. Serostatus of HHV-6A and Epstein-Barr virus was analysed with a bead-based multiplex assay. The concentration of sNfL was analysed with single molecule array technology. The association between HHV-6A serology and sNfL was assessed by stratified t-tests and linear regressions, adjusted for Epstein-Barr virus serostatus and sampling age. Within-pair ratios of HHV-6A seroreactivity and sNfL were calculated for each case and its matched control. To assess the temporal relationship between HHV-6A antibodies and sNfL, these ratios were plotted against the time to the clinical onset of multiple sclerosis and compared using locally estimated scatterplot smoothing regressions with 95% confidence intervals (CI). Samples from 519 matched case-control pairs were included. In cases, seropositivity of HHV-6A was significantly associated with the level of sNfL (+11%, 95% CI 0.2-24%, P = 0.045) and most pronounced in the younger half of the cases (+24%, 95% CI 6-45%, P = 0.007). No such associations were observed among the controls. Increasing seroreactivity against HHV-6A was detectable before the rise of sNfL (significant within-pair ratios from 13.6 years versus 6.6 years before the clinical onset of multiple sclerosis). In this study, we describe the association between HHV-6A antibodies and the degree of axonal injury in the multiple sclerosis prodrome. The findings indicate that elevated HHV-6A antibodies both precede and are associated with a higher degree of axonal injury, supporting the hypothesis that HHV-6A infection may contribute to multiple sclerosis development in a proportion of cases., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)
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- 2024
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11. Latent, Early or Late Human Herpes Virus-6B Expression in Adult Mesial Temporal Lobe Epilepsy: Association of Virus Life Cycle with Inflammatory Cytokines in Brain Tissue and Cerebral Spinal Fluid
- Author
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Jia-Qi, Wang, Hong-Yu, Yang, Xue, Shao, Xin-Yue, Jiang, and Jin-Mei, Li
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Adult ,Life Cycle Stages ,Epilepsy, Temporal Lobe ,Herpesvirus 6, Human ,Interleukin-7 ,General Neuroscience ,Humans ,Animals ,Cytokines ,Brain ,Real-Time Polymerase Chain Reaction - Abstract
Human herpes virus-6B (HHV-6B) was suggested as an important etiologic factor of mesial temporal lobe epilepsy, while the mechanism is still unknown. Here, we aimed to analyze antigens representing latent, early and late HHV-6B infection and the association with inflammatory cytokines in brain tissue and cerebral spinal fluid (CSF) from MTLE patients with HHV-6B-positivity.Nested polymerase chain reaction (nPCR), real-time PCR, immunohistochemistry (IHC) and suspension bead array for cytokines were performed.Nested polymerase chain reaction (nPCR) in brain tissue revealed HHV-6B DNA in 19 of 49 MTLE patients (39%) and 1 of 19 controls (5%) (P 0.001), but not in CSF. ICH showed HHV-6B early antigen (P41) positivity in 3 patients (6%), late antigen (gp116/54/64) positivity in 5 patients (10%), latent antigen (U94) positivity in 8 patients (16%), and multiple antigen (early and late or/and latent) positivity in 9 patients (18%). None of these HHV-6B related proteins were found positive in control brain tissue. PCR revealed significant up-regulation of IL-1a, IL-2 and IL-7 mRNA levels in the brain tissue from MTLE patients expressing early antigens compared to those expressing late, latent, multiple antigens, negative antigens and the controls. Suspension bead array of the CSF confirmed significant up-regulation of IL-1a and IL-7 protein expression from MTLE patients expressing early antigens compared to the other groups.Our finding suggests HHV-6B is a common etiologic agent of MTLE. Different virus life cycle may play an important modifying role in inflammatory biology that warrants further investigation. Though virus DNA is difficult detected in CSF, up-regulation of IL-1a and IL-7 in CSF indicates the two cytokines may be taken as indirect biomarker of HHV-6B infection.
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- 2022
12. Human herpesvirus 6A and 6B and polyomavirus JC and BK infections in renal cell carcinoma and their relationship with p53, p16INK4a, Ki‐67, and nuclear factor‐kappa B expression
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Sepide Namdari, Pei Pei Chong, Abbas Behzad‐Behbahani, Bita Geramizadeh, Ali Dehghani Nazhvani, Zamberi Sekawi, and Ali Farhadi
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Ki-67 Antigen ,Herpesvirus 6, Human ,Virology ,DNA, Viral ,Immunology ,NF-kappa B ,Humans ,Prospective Studies ,Tumor Suppressor Protein p53 ,Carcinoma, Renal Cell ,JC Virus ,Microbiology ,Kidney Neoplasms - Abstract
There are a limited number of studies regarding the involvement of viruses in the development and pathogenesis of renal cell carcinoma (RCC). In this study, we aimed to discover whether human herpesvirus 6A (HHV-6A) and 6B (HHV-6B) and human polyomavirus JC (JCV) and BK (BKV) are associated with RCC and the expression of p53, p16INK4a, Ki-67, and nuclear factor-κB (NF-κB) in patients with RCC. A total of 122 histologically confirmed RCC tissue specimens and 96 specimens of their corresponding peritumoral tissues were included in this prospective study. Nested PCR was performed to amplify viral DNA sequences. Restriction endonuclease analysis was carried out to discriminate between HHV-6A and HHV-6B. p53, p16INK4a, Ki-67, and NF-κB immunostaining data of the studied tissue specimens were available from our previous study. Statistical analysis was performed to demonstrate the potential associations. HHV-6B and JCV were detected in 10.7% and 13.9% of patients with RCC, respectively. We did not detect HHV-6A and BKV in any of RCC tissue specimens. Moreover, no association was found between either of these viruses and RCC. Our study revealed a significant association between HHV-6B and p53 overexpression. No other associations were found between cellular biomarkers p53, p16INK4a, Ki-67, and NF-κB and the studied viruses. The data of this study, though very limited, disprove the involvement of HHV-6A, HHV-6B, BKV, and JCV in the initiation or progression of RCC.
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- 2022
13. Human herpesvirus 6 <scp>DNA</scp> was not detected in a brain specimen from a patient with mesial temporal sclerosis after status epilepticus due to human herpesvirus 6 infection
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Yoshiki Kawamura, Satoshi Maesawa, Shingo Numoto, Ryuta Saito, Tetsushi Yoshikawa, and Akihisa Okumura
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Sclerosis ,Status Epilepticus ,Epilepsy, Temporal Lobe ,Neurology ,Herpesvirus 6, Human ,Humans ,Roseolovirus Infections ,Brain ,Neurology (clinical) ,Seizures, Febrile - Abstract
We performed virological analysis of resected brain tissues from a patient with temporal lobe epilepsy associated with mesial temporal sclerosis after febrile status epilepticus caused by human herpesvirus 6 infection. The patient had febrile status epilepticus at 9 months of age associated with human herpesvirus 6 infection. Magnetic resonance imaging revealed reduced water diffusion in the right temporal lobe and hippocampus. Polymerase chain reaction analysis detected 1.6 × 10
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- 2022
14. Analysis of viral nucleic acids in duodenal biopsies from adult patients with celiac disease
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Marianna Calabretto, Daniele Di Carlo, Francesca Falasca, Laura Mazzuti, Arianna Meacci, Giuseppe Donato, Nicoletta Greco, Laura Mezzatesta, Anna Morrone, Ombretta Turriziani, and Antonio Picarelli
- Subjects
Adult ,Celiac Disease ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Hepatology ,Biopsy ,Herpesvirus 6, Human ,Nucleic Acids ,Cytomegalovirus Infections ,DNA, Viral ,Gastroenterology ,Cytomegalovirus ,Humans - Abstract
The purpose of this study was to investigate the presence of Adenovirus, Epstein-Barr virus (EBV), HHV-6 and cytomegalovirus (CMV) nucleic acids in the gastrointestinal biopsies from active CD patients.Gastrointestinal biopsies of 40 active CD patients and 40 non-CD patients were collected during the endoscopic investigation of gastrointestinal symptoms.HHV-6B was found in 62.5% of CD patients and in 65% of non-CD individuals, whereas the prevalence of EBV-positive samples was 20 and 10%, respectively. Nucleic acids from HHV-6A, CMV and adenovirus were not detected in any group.These data suggest that these viruses may not play a role in the pathogenesis of acute CD, but they do not exclude the possibility that viruses can act as a trigger for the onset of celiac disease.
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- 2022
15. Association between human herpesvirus 6 (HHV-6) and cognitive function in the elderly population in Shenzhen, China
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Chao, Huang, Wei, Liu, Xiaohu, Ren, Yuan, Lv, Lu, Wang, Jia, Huang, Feiqi, Zhu, Desheng, Wu, Li, Zhou, Xinfeng, Huang, and Jianjun, Liu
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China ,Aging ,Cognition ,Alzheimer Disease ,Herpesvirus 6, Human ,Humans ,Roseolovirus Infections ,Geriatrics and Gerontology ,Aged - Abstract
Human herpesvirus 6 (HHV-6) is neurophilic, and its relationship with Alzheimer's disease (AD) remains controversial. This study aimed to examine the relationships between HHV-6 and cognitive abilities in elderly people aged 60 years or above from communities in Shenzhen.We recruited participants from 10 community health service centers in Shenzhen. Participants were divided into case and control groups according to Mini-Mental State Examination (MMSE) scale standards and were included in this study with 1:1 matching based on sex and age (± 3 years). The HHV-6 gene was detected by real-time fluorescent quantitative PCR, and the HHV-6 copy number was quantified.A total of 580 participants (cases, n = 290; controls, n = 290), matched for gender and age was included in this study. A positive HHV-6 test was not associated with a significant difference in global cognitive performance (ORHHV-6 infection significantly associated with orientation, attention and calculation, and language in elderly individuals.
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- 2022
16. Concurrent T-cell/histiocyte-rich large B-cell lymphoma and HHV-6A-infected T-cell proliferation: a diagnostic pitfall.
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Bruehl FK, Norgan AP, Shi M, Rech KL, Ding Y, Pittaluga S, and Yuan J
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- Humans, Histiocytes pathology, Cell Proliferation, T-Lymphocytes pathology, Herpesvirus 6, Human, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse pathology
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- 2023
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17. Cutaneous Findings in Inborn Errors of Immunity: An Immunologist's Perspective.
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Cagdas D, Ayasun R, Gulseren D, Sanal O, and Tezcan I
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- Humans, Diagnosis, Differential, Ambulatory Care Facilities, Biopsy, Herpesvirus 6, Human, Skin Diseases diagnosis
- Abstract
Cutaneous manifestations are common in patients with inborn errors of immunity (IEI)/primary immunodeficiency and could be due to infections, immune dysregulation, or lymphoproliferative/malign diseases. Immunologists accept some as warning signs for underlying IEI. Herein, we include noninfectious/infectious cutaneous manifestations that we come across in rare IEI cases in our clinic and provide a comprehensive literature review. For several skin diseases, the diagnosis is challenging and differential diagnosis is necessary. Detailed disease history and examination play a vital role in reaching a diagnosis, especially if there is a potential underlying IEI. A skin biopsy is sometimes necessary, especially if we need to rule out inflammatory, infectious, lymphoproliferative, and malignant conditions. Specific and immunohistochemical stainings are particularly important when diagnosing granuloma, amyloidosis, malignancies, and infections like human herpes virus-6, human herpes virus-8, human papillomavirus, and orf. Elucidation of mechanisms of IEIs has improved our understanding of their relation to cutaneous findings. In challenging cases, the immunological evaluation may lead the approach when there is a specific primary immunodeficiency diagnosis or at least help to reduce the number of differential diagnoses. Conversely, the response to therapy may provide conclusive evidence for some conditions. This review raises awareness of concomitant lesions and expands the scope of the differential diagnosis of IEI and the spectrum of skin disease therapy by highlighting frequent forms of IEI-associated cutaneous manifestations. The manifestations given here will guide clinicians to plan for alternative use of diverse therapeutics in a multidisciplinary way for skin diseases., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
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- 2023
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18. Chromosome-Specific Human Herpesvirus 6 Integration and Hematologic Malignancies
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Madeleine R. Heldman, Darren J. Wight, Pakorn Aiewsakun, Amr Aswad, Min Fang, Pavitra Roychoudhury, Terry Stevens-Ayers, Keith R. Jerome, Danielle M. Zerr, Alexander L. Greninger, Benedikt B. Kaufer, Michael Boeckh, and Joshua A. Hill
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Virology ,Insect Science ,Hematologic Neoplasms ,Herpesvirus 6, Human ,Virus Integration ,Immunology ,DNA, Viral ,Humans ,Roseolovirus Infections ,Microbiology ,Letter to the Editor ,Chromosomes - Published
- 2023
19. MicroRNA expression profiling of cerebrospinal fluid/serum exosomes in children with human herpesvirus 6-associated encephalitis/encephalopathy by high-throughput sequencing
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Yuka Torii, Jun-ichi Kawada, Kazuhiro Horiba, Toshihiko Okumura, Takako Suzuki, and Yoshinori Ito
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MicroRNAs ,Cellular and Molecular Neuroscience ,Neurology ,Herpesvirus 6, Human ,Virology ,High-Throughput Nucleotide Sequencing ,Humans ,Roseolovirus Infections ,Encephalitis, Viral ,Neurology (clinical) ,Child ,Exosomes - Abstract
Primary human herpesvirus 6 (HHV-6) infection is sometimes accompanied by acute encephalopathy with reduced subcortical diffusion (AED) in immunocompetent children. We investigated exosomal microRNA (miRNA) expression profiles in cerebrospinal fluid (CSF) and sera of patients with HHV-6-associated AED (n = 5) and febrile seizure (FS) (n = 5) using high-throughput sequencing. A total of 176 and 663 miRNAs were identified in CSF and serum exosomes, respectively. Comparative analysis determined that some miRNAs (miR-381-3p, miR-155) were exclusively expressed in the CSF exosomes of AED but not of FS patients, suggesting their potential application as novel diagnostic biomarkers for AED.
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- 2022
20. Confused about Confusion
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Anne M. Spanjaart, Fleur M. van der Valk, Geeske van Rooijen, Matthijs C. Brouwer, Marie J. Kersten, Hematology, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Neurology, ANS - Neuroinfection & -inflammation, Clinical Haematology, and CCA - Cancer Treatment and Quality of Life
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Receptors, Chimeric Antigen ,Herpesvirus 6, Human ,Brain ,Roseolovirus Infections ,General Medicine ,Middle Aged ,Viral Load ,Antiviral Agents ,Immunotherapy, Adoptive ,Magnetic Resonance Imaging ,Diagnosis, Differential ,Limbic Encephalitis ,Humans ,Female ,Lymphoma, Large B-Cell, Diffuse ,Confusion - Published
- 2022
21. Post‐mortem differential diagnosis from COVID‐19: A case of fulminant myocarditis HHV‐6 related
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Franca Del Nonno, Camilla Cecannecchia, Fabrizio Taglietti, Marco Albore, Giorgio Bolino, Roberta Nardacci, and Daniele Colombo
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Pathology ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Myocarditis ,Coronavirus disease 2019 (COVID-19) ,SARS-CoV-2 ,business.industry ,Herpesvirus 6, Human ,Fulminant ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,COVID-19 ,General Medicine ,medicine.disease ,Pathology and Forensic Medicine ,Diagnosis, Differential ,Humans ,Medicine ,Autopsy ,Differential diagnosis ,business ,Letter to the Editor - Published
- 2021
22. Herpesviruses in patients after renal transplantation
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Boldykyz T. Dzhumabaeva, Dmitry S. Tikhomirov, Lyudmila S. Biryukova, Tatiana A. Tupoleva, Igor V. Nesterenko, Natalia V. Purlo, and Dmitry I. Chebоtarev
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Male ,Adult ,human herpes virus type 6 ,History ,Herpesvirus 4, Human ,Endocrinology, Diabetes and Metabolism ,Herpesvirus 6, Human ,viruses ,virus diseases ,kidney transplantation ,General Medicine ,Antiviral Agents ,epstein–barr virus ,Immunoglobulin M ,Superinfection ,Immunoglobulin G ,DNA, Viral ,Cytomegalovirus Infections ,Humans ,Medicine ,Female ,Family Practice ,cytomegalovirus ,Herpesviridae - Abstract
To estimate graft function after kidney transplantation during active herpesviruses or superinfection Materials and methods. The study included 32 patients (men 21, women 11) with end-stage chronic kidney disease. The median age was 43 years. Cytomegalovirus (CMV), EpsteinBarr virus (EBV) and human herpes virus 6 (HHV-6) DNAs were screened by RT-PCR in the donor's transplant biopsy, and recipients peripheral blood and urine after kidney transplantation (KT) on 0, 1, 2, 4, 6, 12 months. Antiviral antibodies (IgM and IgG) were also screened by Enzyme-linked immunoassay analysis (ELISA) along with PCR. The 500 or less copies of viral DNA per 105 nuclear cells or 1 ml of urine was considered as low, more than 1000 copies high.On the first month after KT CMV DNA was detected in 50% of pts., EBV DNA in 40% and HHV-6 DNA in 33%. During first year after KT two or three viruses simultaneously were found in 12 recipients: CMV, EBV, and HHV-6 were detected in 5 recipients; CMV and EBV in 4 patients; CMV and HHV-6 in 2 pts; EBV and HHV-6 in 1 pt. Graft dysfunction was observed in 9 patients with a high concentration of viral DNA of one, two or three viruses simultaneously. An upraise of the concentration of virus DNA (CMV, EBV and HHV 6) was detected primarily in the urine, while in the blood its concentration was less than 500 cop or undetectable. Renal dysfunction was not observed on the background of low concentrations of viral DNA in urine and blood. However, with an increase of DNA concentration, an impaired graft function in 8 of 12 patients appeared. Low viral DNA level proved to be a background for another virus activation or bacterial/fungal superinfection.Graft dysfunction occurs at high viral DNA levels detection during mono-or superinfection. Low viral load can serve as a background for another virus activation and/or bacterial/fungal superinfection.Цель. Оценить функцию почечного трансплантата при сочетанной герпесвирусной инфекции. Материалы и методы. В исследование включены 32 пациента (мужчин 21, женщин 11) с хронической болезнью почек терминальной стадии (ХБПС5). Медиана возраста 43 года. Методом иммуноферментного анализа определяли противовирусные иммуноглобулины, методом полимеразной цепной реакции концентрацию ДНК цитомегаловируса, вируса Эпштейна-Барр (ВЭБ) и вируса герпеса человека 6-го типа (ВГЧ-6) в периферической крови, моче у реципиента до и через 1, 2, 4, 6 мес, 1 год после трансплантации аллогенной почки (ТАП) и в биоптате трансплантата донора. Концентрация ДНК менее 500 коп/105 клеток или в 1 мл мочи считалась низкой, более 1000 коп высокой. Результаты. В 1-й месяц после ТАП выявлена ДНК ЦМВ в 50% случаев, ДНК ВЭБ в 40% и ДНК ВГЧ-6 в 33%. У 12 реципиентов обнаружены одновременно маркеры двух или трех вирусов. Из них у 5 реципиентов ДНК ЦМВ, ВЭБ и ВГЧ-6, у 4 ДНК ЦМВ и ВЭБ, у 2 ДНК ЦМВ и ВГЧ-6, у 1 ВЭБ и ВГЧ-6. Повышение концентрации ДНК выявлялось прежде всего в моче, при этом в крови концентрация оставалась низкой или вообще не определялась. У 9 пациентов наблюдалось нарушение функции трансплантата при высокой концентрации ДНК одного или сразу двух/трех вирусов в моче. При низкой вирусной нагрузке как в моче, так и в крови не отмечалась дисфункция трансплантата, но у 8 из 12 реципиентов на фоне низкой концентрации одного вируса выявлялось повышение концентрации другого или присоединение бактериальной, грибковой инфекции. Заключение. Высокая концентрация ДНК в моче одного или нескольких герпесвирусов указывает на дисфункцию почечного трансплантата. Низкая вирусная нагрузка может служить фоном для присоединения другой вирусной и бактериальной инфекции.
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- 2021
23. Association of HHV-6 With Outcomes in CMV-seronegative Liver Transplant Recipients With CMV-seropositive Donors Receiving Preemptive Antiviral Therapy
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Nina Singh, Meei Li Huang, Raymund R. Razonable, Marilyn M. Wagener, G. Marshall Lyon, Fernanda P. Silveira, Drew J. Winston, Ajit P. Limaye, and Keith R. Jerome
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medicine.medical_specialty ,Herpesvirus 6, Human ,Cytomegalovirus ,Viremia ,Antiviral Agents ,Gastroenterology ,law.invention ,Randomized controlled trial ,law ,Internal medicine ,Humans ,Medicine ,Ganciclovir ,Transplantation ,business.industry ,Area under the curve ,virus diseases ,Valganciclovir ,medicine.disease ,Transplant Recipients ,Liver Transplantation ,Real-time polymerase chain reaction ,Cytomegalovirus Infections ,Population study ,business ,Viral load ,medicine.drug - Abstract
BACKGROUND Risk factors, virological parameters, and outcomes associated with HHV-6 viremia in high-risk donor CMV-seropositive and recipient CMV-seronegative (D+R-) liver transplant recipients in the current era are incompletely defined. METHODS The study population consisted of patients in the preemptive therapy (PET) arm of a randomized, controlled trial of PET versus valganciclovir prophylaxis for CMV prevention in D+R- liver transplant recipients. Weekly blood samples through 100 d in the PET group were tested for HHV-6 viremia using a real-time quantitative polymerase chain reaction. Assessments included virological characteristics and relationship with CMV, risk factors, and impact of HHV-6 viremia with outcomes through 12 mo posttransplant. RESULTS HHV-6 viremia at any level developed in 42% (40 of 96). Older patient age (P = 0.03), longer hospitalization (P = 0.015), and ICU stay at transplantation (P = 0.029) were significantly associated with high-grade viremia. Concurrent HHV-6 and CMV viremia was associated with earlier onset of HHV-6 viremia (P = 0.004), higher HHV-6 area under the curve (P = 0.043), and higher peak HHV-6 viral load (P = 0.006) versus HHV-6 viremia alone. High-grade viremia was independently associated with biopsy-proven rejection within 12 mo (P = 0.045) posttransplant. CONCLUSIONS Among D+R- liver transplant recipients receiving valganciclovir as PET, high-grade HHV-6 viremia was associated with increased age and critical illness in ICU at time of transplant and was independently associated with allograft rejection.
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- 2021
24. Presence and clinical impact of human herpesvirus‐6 infection in patients with moderate to critical coronavirus disease‐19
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Katia Lino, Lilian Santos Alves, Thalia Medeiros, Vanessa Salete de Paula, Andrea Alice da Silva, Jorge Reis Almeida, Cintia Fernandes de Souza, and Jéssica Vasques Raposo
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medicine.medical_specialty ,Short Communication ,Herpesvirus 6, Human ,viruses ,Short Communications ,Roseolovirus Infections ,Pilot Projects ,Disease ,herpesvirus‐6 ,COVID‐19 ,Virology ,Internal medicine ,Diabetes mellitus ,Epidemiology ,medicine ,Humans ,HHV‐6 ,Prospective Studies ,Prospective cohort study ,biology ,Coinfection ,SARS-CoV-2 ,business.industry ,Medical record ,COVID-19 ,virus diseases ,Cancer ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,medicine.disease ,Infectious Diseases ,Human herpesvirus 6 ,business - Abstract
Human herpesvirus‐6 (HHV‐6) may cause serious diseases in immunocompromised individuals. SARS‐CoV‐2/HHV‐6 coinfection has been emphasized in previous works, mostly case reports, small series, or epidemiological studies, but few are known about its real clinical outcomes. Here we present a real‐world pilot study aiming to understand the frequency and the clinical impact of HHV‐6 coinfection in moderate to critically ill patients hospitalized due to COVID‐19. SARS‐CoV‐2 and HHV‐6 were evaluated in nasopharyngeal samples at the hospital admission of suspected COVID‐19 patients. From 173 consecutive cases, 60 were SARS‐CoV‐2 positive and 13/60 (21.7%) were HHV‐6 positive after identified as the HHV‐6B species by a Sanger sequencing. The SARS‐CoV‐2+/HHV‐6+ group was younger but not significant for cardiovascular diseases, diabetes, obesity, and cancer, but significant among therapeutic immunosuppressed patients (as systemic lupus erythematosus and kidney transplant patients). In the medical records, only sparse data on cutaneous or neurological manifestations were found. Biochemical and hematological data showed only a trend towards hyperferritinemic status and lymphopenia. In conclusion, despite the impressive high frequency of HHV‐6 coinfection in SARS‐CoV‐2 positive cases, it did not impact general mortality. We suggest larger future prospective studies to better elucidate the influence of HHV‐6 reactivation in cases of COVID‐19, designed to specific assessment of clinical outcomes and viral reactivation mechanisms.
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- 2021
25. Analysis of herpesvirus infection and genome single nucleotide polymorphism risk factors in multiple sclerosis, Volga federal district, Russia
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Vera, Lezhnyova, Yuriy, Davidyuk, Asia, Mullakhmetova, Maria, Markelova, Alexander, Zakharov, Svetlana, Khaiboullina, and Ekaterina, Martynova
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Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Multiple Sclerosis ,Risk Factors ,Herpesvirus 6, Human ,Immunology ,Humans ,Immunology and Allergy ,Antibodies, Viral ,Polymorphism, Single Nucleotide ,Russia - Abstract
Multiple sclerosis (MS) is a heterogeneous disease where herpesvirus infection and genetic predisposition are identified as the most consistent risk factors. Serum and blood samples were collected from 151 MS and 70 controls and used to analyze circulating antibodies for, and DNA of, Epstein Barr virus (EBV), human cytomegalovirus (HCMV), human herpes virus 6 (HHV6), and varicella zoster virus (VZV). The frequency of selected single nucleotide polymorphisms (SNPs) in MS and controls were studied. Herpesvirus DNA in blood samples were analyzed using qPCR. Anti-herpesvirus antibodies were detected by ELISA. SNPs were analyzed by the allele-specific PCR. For statistical analysis, Fisher exact test, odds ratio and Kruskall–Wallis test were used; pCD58 gene and G allele in rs929230 of CD6 gene in MS as compared to controls. Fatigue symptom was linked to AC and AA genotype in rs12044852 of CD58 gene. An interesting observation was finding higher frequency of GG genotype in rs12722489 of IL2RA and T allele in rs1535045 of CD40 genes in patient having anti-HHV6 antibodies. A link was found between having anti-VZV antibodies in MS and CC genotype in rs1883832 of CD40 gene.
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- 2022
26. Studying the Interactions of U24 from HHV-6 in Order to Further Elucidate Its Potential Role in MS
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Keng-Shuo Pi, Daria Bortolotti, Yurou Sang, Giovanna Schiuma, Silvia Beltrami, Sabrina Rizzo, Alessandra Bortoluzzi, Eleonora Baldi, A. Louise Creagh, Charles A. Haynes, Roberta Rizzo, and Suzana K. Straus
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Multiple Sclerosis ,Infectious Diseases ,Herpesvirus 6, Human ,Virology ,Humans ,Roseolovirus Infections ,Phosphorylation ,Nuclear Magnetic Resonance, Biomolecular ,human herpes virus ,Roseolovirus ,Fyn-SH3 ,Nedd4L ,multiple sclerosis ,phosphorylation ,natural killer cells ,Killer Cell Immunoglobulin Like Receptor 2DL2 - Abstract
A number of studies have suggested that human herpesvirus 6A (HHV-6A) may play a role in multiple sclerosis (MS). Three possible hypotheses have been investigated: (1) U24 from HHV-6A (U24-6A) mimics myelin basic protein (MBP) through analogous phosphorylation and interaction with Fyn-SH3; (2) U24-6A affects endocytic recycling by binding human neural precursor cell (NPC) expressed developmentally down-regulated protein 4-like WW3* domain (hNedd4L-WW3*); and (3) MS patients who express Killer Cell Immunoglobulin Like Receptor 2DL2 (KIR2DL2) on natural killer (NK) cells are more susceptible to HHV-6 infection. In this contribution, we examined the validity of these propositions by investigating the interactions of U24 from HHV-6B (U24-6B), a variant less commonly linked to MS, with Fyn-SH3 and hNedd4L-WW3* using heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR) titrations and isothermal titration calorimetry (ITC). In addition, the importance of phosphorylation and the specific role of U24 in NK cell activation in MS patients were examined. Overall, the findings allowed us to shed light into the models linking HHV-6 to MS and the involvement of U24.
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- 2022
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27. Human herpesvirus 6 and epilepsy
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Bridgette Jeanne Billioux, Steven Jacobson, John D. Heiss, Kareem A. Zaghloul, William H. Theodore, Sara K. Inati, Emily C. Leibovitch, and William D. Gaillard
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focal epilepsy ,Pathology ,medicine.medical_specialty ,mesial temporal sclerosis ,viruses ,Herpesvirus 6, Human ,H&E stain ,Real-Time Polymerase Chain Reaction ,Epilepsy ,Febrile seizure ,medicine ,Short Research Article ,Humans ,HHV‐6 ,RC346-429 ,biology ,Glial fibrillary acidic protein ,business.industry ,virus diseases ,Cortical dysplasia ,medicine.disease ,biology.organism_classification ,Short Research Articles ,Neurology ,DNA, Viral ,biology.protein ,Human herpesvirus 6 ,Neurology (clinical) ,Neurology. Diseases of the nervous system ,NeuN ,business ,Tomography, X-Ray Computed ,Encephalitis - Abstract
We investigated the association between human herpesvirus 6 (HHV‐6) and mesial temporal sclerosis (MTS) in 87 patients who had surgery for drug‐resistant epilepsy. Fifty‐four had MTS, 22 focal cortical dysplasia (FCD), four tumors, three vascular malformations, and three a history of encephalitis. We extracted DNA from fresh brain tissue immediately after surgery and performed viral detection with quantitative real‐time polymerase chain reaction (PCR) or digital droplet PCR specific for HHV‐6A and HHV‐6B. Tissue was studied with standard clinical techniques, including hematoxylin and eosin, glial fibrillary acidic protein, and NeuN stains. Twenty‐nine of 54 patients with MTS, six of 23 with focal cortical dysplasia (FCD), and one of three with a history of encephalitis were positive for HHV‐6 (P
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- 2021
28. Regarding investigation of prognostic factors for HHV 6/7- associated acute encephalopathy.
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Wojtara MS
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- Humans, Prognosis, Herpesvirus 6, Human, Herpesvirus 7, Human, Brain Diseases, Roseolovirus Infections complications
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Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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- 2023
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29. Reply to the letter "Regarding investigation of prognostic factors for HHV 6/7-associated acute encephalopathy".
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Watanabe Y, Odaka M, Motoi H, Oyama Y, Shiga K, and Ito S
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- Humans, Prognosis, Herpesvirus 6, Human, Herpesvirus 7, Human, Brain Diseases, Encephalitis, Viral
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Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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- 2023
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30. Current Perspectives on the Management of Herpesvirus Infections in Solid Organ Transplant Recipients.
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Malahe SRK, van Kampen JJA, Manintveld OC, Hoek RAS, den Hoed CM, Baan CC, Kho MML, and Verjans GMGM
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- Humans, Transplant Recipients, Organ Transplantation adverse effects, Herpesviridae Infections drug therapy, Herpesviridae Infections prevention & control, Herpesvirus 6, Human, Herpes Simplex
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Solid organ transplant recipients (SOTRs) are at high risk of human herpesvirus (HHV)-related morbidity and mortality due to the use of immunosuppressive therapy. We aim to increase awareness and understanding of HHV disease burden in SOTRs by providing an overview of current prevention and management strategies as described in the literature and guidelines. We discuss challenges in both prevention and treatment as well as future perspectives.
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- 2023
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31. An unusual skin eruption related to HHV-7 infection in a 14-year-old girl.
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Caroppo F, Gratteri F, Deotto ML, Salmaso R, and Belloni Fortina A
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- Female, Humans, Adolescent, Herpesvirus 7, Human, Exanthema diagnosis, Exanthema etiology, Herpesvirus 6, Human, Roseolovirus Infections
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- 2023
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32. ATF1 Restricts Human Herpesvirus 6A Replication via Beta Interferon Induction
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Salma Aktar, Jun Arii, Thi Thu Huong Nguyen, Jing Rin Huang, Mitsuhiro Nishimura, and Yasuko Mori
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Activating Transcription Factor 1 ,herpesviruses ,Herpesvirus 6, Human ,Immunology ,Cellular Response to Infection ,Interferon-beta ,Virus Replication ,Microbiology ,HHV-6 ,interferons ,Gene Knockout Techniques ,Virology ,Insect Science ,transcription factors ,ATF1 ,gene expression ,Humans ,Cyclic AMP Response Element-Binding Protein - Abstract
The stimulus-induced cAMP response element (CRE)-binding protein (CREB) family of transcription factors bind to CREs to regulate diverse cellular responses, including proliferation, survival, and differentiation. Human herpesvirus 6A (HHV-6A), which belongs to the Betaherpesvirinae subfamily, is a lymphotropic herpesvirus frequently found in patients with neuroinflammatory diseases. Previous reports implicated the importance of CREs in the HHV-6A life cycle, although the effects of the binding of transcription factors to CREs in viral replication have not been fully elucidated. In this study, we analyzed the role of the CREB family of transcription factors during HHV-6A replication. We found that HHV-6A infection enhanced phosphorylation of the CREB family members CREB1 and activating transcription factor 1 (ATF1). Knockout (KO) of CREB1 or ATF1 enhanced viral gene expression and viral replication. The increase in viral yields in supernatants from ATF1-KO cells was greater than that in supernatants from CREB1-KO cells. Transcriptome sequencing (RNA-seq) analysis showed that sensors of the innate immune system were downregulated in ATF1-KO cells, and mRNAs of beta interferon (IFN-β) and IFN-regulated genes were reduced in these cells infected with HHV-6A. IFN-β treatment of ATF1-KO cells reduced progeny viral yields significantly, suggesting that the enhancement of viral replication was caused by a reduction of IFN-β. Taken together, our results suggest that ATF1 is activated during HHV-6A infection and restricts viral replication via IFN-β induction. IMPORTANCE Human herpesvirus 6A (HHV-6A) is a ubiquitous herpesvirus implicated in Alzheimer’s disease, although its role in its pathogenesis has not been confirmed. Here, we showed that the transcription factor ATF1 restricts HHV-6A replication, mediated by IFN-β induction. Our study provides new insights into the role of ATF1 in innate viral immunity and reveals the importance of IFN-β for regulation of HHV-6A replication, which possibly impairs HHV-6A pathogenesis.
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- 2022
33. Persistent HHV-6 DNAemia in a Patient Presenting With Meningoencephalitis
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Amandeep Sandhu, Jason Kim, Louis M. Bell, Soma Jyonouchi, Lisa N. Akhtar, and Sarah E. Henrickson
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Meningoencephalitis ,Herpesvirus 6, Human ,Pediatrics, Perinatology and Child Health ,Cytomegalovirus Infections ,DNA, Viral ,Humans ,Roseolovirus Infections - Published
- 2022
34. Epstein–Barr Virus and Human Herpesvirus-6 Reactivation in Acute COVID-19 Patients
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Bailey Brooks, Christina Tancredi, Yufeng Song, Alemu Tekewe Mogus, Meei-Li W. Huang, Haiying Zhu, Tuan L. Phan, Harrison Zhu, Alexandra Kadl, Judith Woodfolk, Keith R. Jerome, and Steven L. Zeichner
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Inflammation ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Infectious Diseases ,Virology ,Herpesvirus 6, Human ,COVID-19 ,SARS-CoV-2 ,Epstein–Barr virus ,EBV ,Human Herpesvirus-6 ,HHV-6 ,reactivation ,Herpesvirus 8, Human ,Humans ,Inflammation Mediators - Abstract
Beyond their pulmonary disease, many COVID-19 patients experience a complex constellation of characteristics, including hyperinflammatory responses, autoimmune disorders, and coagulopathies. However, the pathogenesis of these aspects of COVID-19 is obscure. More than 90% of people are latently infected with the lymphotropic herpesviruses Epstein–Barr Virus (EBV) and/or Human Herpesvirus-6 (HHV-6). Some of the inflammatory features of COVID-19 resemble clinical syndromes seen during EBV and HHV-6 infection, and these latent viruses can be reactivated by inflammatory mediators. We hypothesized that EBV and HHV-6 reactivation might be a common feature of early COVID-19, particularly in patients with more inflammation. We tested for EBV and HHV-6 reactivation in 67 patients acutely hospitalized with COVID-19 using previously validated quantitative PCR assays on the plasma. In our cohort, we found that 15/67 (22.4%) patients had detectable EBV and 3/67 (4.5%) had detectable HHV-6. This frequency of activation is somewhat more than the frequency reported for some healthy cohorts, such as blood donors and other healthy control cohorts. There was no association between EBV or HHV-6 and markers indicative of more inflammatory disease. We conclude that EBV and HHV-6 activation at about day 7 of hospitalization occurred in a modest fraction of our cohort of COVID-19 patients and was not associated with high levels of inflammation. In the modest fraction of patients, EBV and HHV-6 reactivation could contribute to some features of acute disease and pre-disposition to post-acute sequelae in a subset of patients.
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- 2022
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35. Peripheral CD5+ CD10+ B-cell proliferation with atypical morphology attributable to human herpesvirus 6 infection following umbilical cord blood transplantation
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Alban Canali, Jean‐Baptiste Rieu, and Barbara J. Bain
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Science & Technology ,Herpesvirus 6, Human ,Immunology ,Humans ,Neprilysin ,Hematology ,Cord Blood Stem Cell Transplantation ,CD5 Antigens ,Fetal Blood ,Life Sciences & Biomedicine ,1102 Cardiorespiratory Medicine and Haematology ,Cell Proliferation ,Immunophenotyping - Published
- 2022
36. Late‐onset intrauterine growth restriction and HHV‐6 infection: A pilot study
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Cristina Taliento, Giovanni Lanza, Roberta Rizzo, Giovanna Schiuma, Pantaleo Greco, Silvia Beltrami, Erica Santi, Roberta Gafà, Amerigo Vitagliano, Daria Bortolotti, Valentina Gentili, and Sabrina Rizzo
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Adult ,Male ,Placenta Diseases ,placenta ,Herpesvirus 6, Human ,HLA-G ,Roseolovirus Infections ,Physiology ,Pilot Projects ,Late onset ,NO ,Late Onset Disorders ,HHV-6 ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,IUGR ,Virology ,Placenta ,medicine ,Humans ,Childbirth ,030212 general & internal medicine ,reproductive and urinary physiology ,Retrospective Studies ,HLA-G Antigens ,Fetus ,Fetal Growth Retardation ,business.industry ,Infant, Newborn ,medicine.disease ,Infectious Diseases ,medicine.anatomical_structure ,embryonic structures ,Gestation ,Immunohistochemistry ,Female ,030211 gastroenterology & hepatology ,business - Abstract
Background Late onset intra-uterine growth restriction (IUGR) refers to impaired growth and development of the fetus, characterized by placental morphological abnormalities that affect the fetus supply of nutrients. Human Leukocyte Antigen-G (HLA-G) is physiologically expressed during pregnancy, but in normal placenta decreased during the last weeks of gestation possibly inducing childbirth. Several viruses involved in congenital infection, such as herpesviruses, exploit HLA-G expression as an immune-escape mechanism. To date, despite different congenital herpetic infections have been associated with late IUGR, no direct implication of HHV-6 infection, has been reported. Methods We evaluated HLA-G expression and HHV-6 infection in 11 placentas from late onset IUGR newborns and 11 placentas from uncomplicated pregnancies by histopathological and immunohistochemistry analysis. Results We found higher levels of HLA-G expression and HHV-6 presence in IUGR placenta samples compared with control placenta samples. Conclusions We report HHV-6 staining in IUGR placenta samples, characterized by high HLA-G expression. These preliminary data suggest a possible involvement of HHV-6 infection in HLA-G deregulation that might affect vessel remodeling and prevent the correct pregnancy outcome in IUGR condition. This article is protected by copyright. All rights reserved.
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- 2021
37. High antibody levels against human herpesvirus-6A interact with lifestyle factors in multiple sclerosis development
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Lars Alfredsson, Anna Karin Hedström, Jing Wu, Tomas Olsson, Anna Fogdell-Hahn, Tim Waterboer, Rasmus Gustafsson, Jan Hillert, and Elin Engdahl
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0303 health sciences ,Multiple Sclerosis ,Human Herpesvirus 6A ,Ultraviolet Rays ,business.industry ,Herpesvirus 6, Human ,Multiple sclerosis ,Antibody level ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Lifestyle factors ,Neurology ,Case-Control Studies ,Immunology ,Humans ,Medicine ,Neurology (clinical) ,business ,Life Style ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
Background: Infection with human herpesvirus 6A (HHV-6A) has been suggested to increase multiple sclerosis (MS) risk. However, potential interactions between HHV-6A and environmental/lifestyle risk factors for MS have not previously been studied. Methods: We used two Swedish population-based case-control studies comprising 5993 cases and 5995 controls. Using logistic regression models, subjects with different HHV-6A antibody levels, environmental exposures, and lifestyle habits were compared regarding MS risk, by calculating odds ratios (ORs) with 95% confidence intervals (CIs). Potential interactions between high HHV-6A antibody levels and common environmental exposures and lifestyle factors were evaluated on the additive scale. Results: High HHV-6A antibody levels were associated with increased risk of developing MS (OR = 1.5, 95% CI = 1.4–1.6). Regarding MS risk, significant interactions were observed between high HHV-6A antibody levels and both smoking (attributable proportion (AP) = 0.2, 95% CI = 0.1–0.3), low ultraviolet radiation (UVR) exposure (AP = 0.3, 95% CI = 0.1–0.4), and low vitamin D levels (AP = 0.3, 95% CI = 0.0–0.6). Conclusion: High HHV-6A antibody levels are associated with increased MS risk and act synergistically with common environmental/lifestyle risk factors for MS. Further research is needed to investigate potential mechanisms underlying the interactions presented in this study.
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- 2021
38. Severe herpes virus 6 interstitial pneumonia in an infant with three variants in genes predisposing to lung disease
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Domenico Umberto De Rose, Ferdinando Savignoni, Piermichele Paolillo, Luana Coltella, Sabrina Rossi, Rossella Iannotta, Simona Lozzi, Simonetta Picone, Antonio Novelli, Renato Cutrera, Irma Capolupo, Maria Cristina Digilio, Cinzia Auriti, Andrea Dotta, Teresa Pianini, and Livia Piccioni
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Ganciclovir ,Heterozygote ,Herpesvirus 6, Human ,Pneumonia, Viral ,Roseolovirus Infections ,03 medical and health sciences ,Fatal Outcome ,0302 clinical medicine ,Virology ,medicine ,Humans ,Genetic Predisposition to Disease ,030212 general & internal medicine ,Lung ,Respiratory distress ,biology ,medicine.diagnostic_test ,business.industry ,Infant, Newborn ,Genetic Variation ,Hydroxychloroquine ,Viral Load ,biology.organism_classification ,medicine.disease ,Mucin-5B ,Cytoskeletal Proteins ,Pneumonia ,Infectious Diseases ,medicine.anatomical_structure ,Bronchoalveolar lavage ,Immunology ,Female ,030211 gastroenterology & hepatology ,Human herpesvirus 6 ,Differential diagnosis ,Lung Diseases, Interstitial ,business ,Microtubule-Associated Proteins ,medicine.drug - Abstract
Infections due to human herpesvirus 6 (HHV-6) are frequent during early childhood. Usually, they have a favorable clinical course. Conversely, HHV-6 congenital infections occur in about 1% of neonates and may present with more severe clinical pictures. HHV-6 can be found in lung tissues and bronchoalveolar lavage (BAL) samples from patients with pneumonia and in immunocompromised patients can cause mild to severe pneumonia. In neonates, the role of HHV-6 in the genesis of severe pneumonia is poorly defined still now. We describe a healthy infant with a late-onset (15 days of life) severe interstitial pneumonia and heavy HHV-6 genome load, persistently detected in its BAL fluid. The baby underwent high-frequency oscillatory ventilation, hydroxychloroquine, steroids, and ganciclovir for 6 weeks and at 9 months she died. Next-generation sequencing of genes known to cause neonatal respiratory insufficiency revealed the presence of a "probably pathogenetic" heterozygous variant in the autosomal recessive DRC1 gene, a heterozygous variant of unknown significance (VUS) in the autosomal recessive RSPH9 gene, and a heterozygous VUS in the autosomal recessive MUC5B gene. HHV-6 infection should be considered in the differential diagnosis of late-onset severe respiratory distress in neonates and the co-occurrence of genetic predisposing factors or modifiers should be tested by specific molecular techniques. The intensity of HHV-6 genome load in BAL fluid could be an indicator of the response to antiviral therapy.
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- 2021
39. High incidence of Epstein–Barr virus, cytomegalovirus, and human-herpes virus-6 reactivations in critically ill patients with COVID-19
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L. Robriquet, D. Hober, B. Garcia, A.-S. Moreau, S. Six, A.J. Simonnet, Mercé Jourdain, A. El Kalioubie, and I. Engelmann
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Adult ,Male ,Herpesvirus 4, Human ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Critical Illness ,Herpesvirus 6, Human ,viruses ,Epstein -Barr virus ,Congenital cytomegalovirus infection ,Cytomegalovirus ,Viremia ,medicine.disease_cause ,Article ,Virus ,law.invention ,law ,Internal medicine ,medicine ,Humans ,Aged ,Retrospective Studies ,Coronavirus ,Aged, 80 and over ,SARS-CoV-2 ,business.industry ,Incidence ,virus diseases ,Middle Aged ,medicine.disease ,Intensive care unit ,Epstein–Barr virus ,Intensive Care Units ,Infectious Diseases ,Concomitant ,Latent Infection ,Female ,Virus Activation ,France ,Covid-19 ,business - Abstract
Background Systemic reactivation of herpesviruses may occur in intensive care unit (ICU) patients and is associated with morbidity and mortality. Data on severe Coronavirus disease-19 (COVID-19) and concomitant reactivation of herpesviruses are lacking. Methods We selected patients admitted to ICU for confirmed COVID-19 who underwent systematic testing for Epstein–Barr virus (EBV), cytomegalovirus (CMV) and human-herpes virus-6 (HHV-6) DNAemia while in the ICU. We retrospectively analysed frequency, timing, duration and co-occurrence of viral DNAemia. Results Thirty-four patients were included. Viremia with EBV, CMV, and HHV-6 was detected in 28 (82%), 5 (15%), and 7 (22%) patients, respectively. EBV reactivation occurred early after ICU admission and was associated with longer ICU length-of-stay. Conclusions While in the ICU, critically ill patients with COVID-19 are prone to develop reactivations due to various types of herpesviruses.
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- 2021
40. The preceding hyponatremia is a useful hallmark for the diagnosis of HHV-6 encephalitis after allogeneic hematopoietic stem cell transplantation
- Author
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Shota Yoshida, Takahide Ara, Kohei Okada, Yuto Mori, Shihori Tsukamoto, Naoki Miyashita, Kohei Kasahara, Ko Ebata, Junko Iwasaki, Shojiro Takahashi, Akio Shigematsu, Koichiro Minauchi, Naoki Kobayashi, Masahiro Ogasawara, Masahiro Imamura, Takanori Teshima, and Shuichi Ota
- Subjects
Transplantation ,Herpesvirus 6, Human ,DNA, Viral ,Hematopoietic Stem Cell Transplantation ,Humans ,Transplantation, Homologous ,Roseolovirus Infections ,Hematology ,Encephalitis, Viral ,Hyponatremia - Abstract
Human herpes virus-6 (HHV-6) encephalitis is one of the life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Early diagnosis and intervention are important for the prevention of poor prognosis and sequelae. Although hyponatremia is known to be associated with HHV-6 encephalitis, it is unclear whether the preceding hyponatremia is a useful hallmark for the diagnosis of HHV-6 encephalitis. We retrospectively reviewed 134 consecutive patients who underwent allo-HSCT at our institution and evaluated the relationship between HHV-6 encephalitis and hyponatremia. Interestingly, 7 (50%) of 14 patients who developed HHV-6 encephalitis presented hyponatremia within a week before the onset of HHV-6 encephalitis. On the other hand, only 14 (11.7%) out of 120 patients without HHV-6 encephalitis developed hyponatremia. Hyponatremia, treating as a time-dependent covariate, was significantly correlated with the incidence of HHV-6 encephalitis. Moreover, the diagnostic accuracy analysis showed that the coexistence of hyponatremia and central nerve system (CNS) dysfunction strongly suggests HHV-6 encephalitis. In conclusion, our study suggests the likelihood of HHV-6 encephalitis significantly increases in the patients with CNS dysfunction following hyponatremia after allo-HSCT and this combination may help in early diagnosis and intervention of HHV-6 encephalitis after allo-HSCT.
- Published
- 2022
41. EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities
- Author
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Brandon S. Cox, Khaled Alharshawi, Irene Mena-Palomo, William P. Lafuse, and Maria Eugenia Ariza
- Subjects
Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Fatigue Syndrome, Chronic ,Herpesvirus 6, Human ,Humans ,Roseolovirus Infections ,Cell Differentiation ,T-Lymphocytes, Helper-Inducer ,General Medicine ,Pyrophosphatases - Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, debilitating, multisystem illness of unknown etiology for which no cure and no diagnostic tests are available. Despite increasing evidence implicating EBV and human herpesvirus 6A (HHV-6A) as potential causative infectious agents in a subset of patients with ME/CFS, few mechanistic studies address a causal relationship. In this study we examined a large ME/CFS cohort and controls and demonstrated a significant increase in activin A and IL-21 serum levels, which correlated with seropositivity for antibodies against the EBV and HHV-6 protein deoxyuridine triphosphate nucleotidohydrolase (dUTPases) but no increase in CXCL13. These cytokines are critical for T follicular helper (TFH) cell differentiation and for the generation of high-affinity antibodies and long-lived plasma cells. Notably, ME/CFS serum was sufficient to drive TFH cell differentiation via an activin A-dependent mechanism. The lack of simultaneous CXCL13 increase with IL-21 indicates impaired TFH function in ME/CFS. In vitro studies revealed that virus dUTPases strongly induced activin A secretion while in vivo, EBV dUTPase induced the formation of splenic marginal zone B and invariant NKTFH cells. Together, our data indicate abnormal germinal center (GC) activity in participants with ME/CFS and highlight a mechanism by which EBV and HHV6 dUTPases may alter GC and extrafollicular antibody responses.
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- 2022
42. Investigation of the Involvement of HHV-6 Encoded Viral Chemokine Receptors in Autoimmune Thyroiditis Development
- Author
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Alina Sultanova, Maksims Cistjakovs, Liba Sokolovska, Egils Cunskis, and Modra Murovska
- Subjects
Microbiology (medical) ,General Immunology and Microbiology ,Ecology ,Physiology ,Herpesvirus 6, Human ,Thyroiditis, Autoimmune ,Cell Biology ,Antibodies, Viral ,Autoimmune Diseases ,Infectious Diseases ,Immunoglobulin M ,Immunoglobulin G ,Genetics ,Leukocytes, Mononuclear ,Humans ,Receptors, Virus ,Receptors, Chemokine - Abstract
Human herpesvirus-6 (HHV-6) contains two genes (U12 and U51) that encode putative homologues of human G-protein-coupled receptors like CCR1, CCR3, and CCR5. It has been shown that these viral proteins can be expressed on the surface of epithelial and some peripheral blood mononuclear cells, suggesting that they could potentially induce autoimmunity. We aimed to investigate the possibility of HHV-6 encoded viral chemokine receptors (U12 and U51) involvement in autoimmune thyroiditis (AIT) development by detecting viral peptide specific antibodies in AIT patient samples. Seventy-nine AIT patients whose thyroid tissues were shown to be positive for HHV-6 and 32 blood donors were enrolled in this study. Twenty-eight synthetic peptides derived from HHV-6 U12 and U51 proteins' amino acid sequences, as well as recombinant human CCR1, CCR3, and CCR5 proteins were used in suspension multiplex immunological assay to detect specific IgG and IgM antibodies. HHV-6 peptide specific IgG and IgM antibodies were found in patients' samples. AIT patients' samples were found to be more frequently positive for peptide IgGs in comparison to control group's samples. Even though peptide antibody cross-reactivity with human CCRs was not demonstrated, our results show a new immunogenic HHV-6 antigen-a possible new player in the HHV-6 induced autoimmunity exacerbation.
- Published
- 2022
43. Saliva antibody-fingerprint of reactivated latent viruses after mild/asymptomatic COVID-19 is unique in patients with myalgic-encephalomyelitis/chronic fatigue syndrome
- Author
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Eirini, Apostolou, Muhammad, Rizwan, Petros, Moustardas, Per, Sjögren, Bo Christer, Bertilson, Björn, Bragée, Olli, Polo, and Anders, Rosén
- Subjects
Fatigue Syndrome, Chronic ,Post-Acute COVID-19 Syndrome ,SARS-CoV-2 ,Herpesvirus 6, Human ,Immunoglobulin G ,Endogenous Retroviruses ,Immunoglobulin A, Secretory ,Humans ,COVID-19 ,Saliva ,Antibodies, Viral - Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease considered to be triggered by viral infections in a majority of cases. Symptoms overlap largely with those of post-acute sequelae of COVID-19/long-COVID implying common pathogenetic mechanisms. SARS-CoV-2 infection is risk factor for sustained latent virus reactivation that may account for the symptoms of post-viral fatigue syndromes. The aim of this study was first to investigate whether patients with ME/CFS and healthy donors (HDs) differed in their antibody response to mild/asymptomatic SARS-CoV-2 infection. Secondly, to analyze whether COVID-19 imposes latent virus reactivation in the cohorts.Anti-SARS-CoV-2 antibodies were analyzed in plasma and saliva from non-vaccinated ME/CFS (n=95) and HDs (n=110) using soluble multiplex immunoassay. Reactivation of human herpesviruses 1-6 (HSV1, HSV2, VZV, EBV, CMV, HHV6), and human endogenous retrovirus K (HERV-K) was detected by anti-viral antibody fingerprints in saliva.At 3-6 months after mild/asymptomatic SARS-CoV-2 infection, virus-specific antibodies in saliva were substantially induced signifying a strong reactivation of latent viruses (EBV, HHV6 and HERV-K) in both cohorts. In patients with ME/CFS, antibody responses were significantly stronger, in particular EBV-encoded nuclear antigen-1 (EBNA1) IgG were elevated in patients with ME/CFS, but not in HDs. EBV-VCA IgG was also elevated at baseline prior to SARS-infection in patients compared to HDs.Our results denote an altered and chronically aroused anti-viral profile against latent viruses in ME/CFS. SARS-CoV-2 infection even in its mild/asymptomatic form is a potent trigger for reactivation of latent herpesviruses (EBV, HHV6) and endogenous retroviruses (HERV-K), as detected by antibody fingerprints locally in the oral mucosa (saliva samples). This has not been shown before because the antibody elevation is not detected systemically in the circulation/plasma.
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- 2022
44. Detection and quantification of Epstein-Barr virus, cytomegalovirus, and human herpesvirus-6 in stomach frozen tissue of chronic gastritis and gastric cancer patients
- Author
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Behrang Sarshari, Seyed Reza Mohebbi, Mehrdad Ravanshad, Shabnam Shahrokh, Hamid Asadzadeh Aghdaei, and Mohammad Reza Zali
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Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Stomach Neoplasms ,Virology ,Gastritis ,Herpesvirus 6, Human ,Immunology ,Cytomegalovirus Infections ,DNA, Viral ,Cytomegalovirus ,Humans ,Microbiology - Abstract
Human herpes viruses (HHVs) are among the most common infectious agents detected in the gastrointestinal tract that might be involved in oncogenesis and other gastrointestinal disorders. Although the link between the Epstein-Barr virus (EBV) and gastric cancer (GC) has been established, the role of the viruses in various stomach diseases remains unknown. The frequencies and viral copy number of EBV, cytomegalovirus (CMV), and human herpesvirus 6 (HHV-6) among 50 gastric cancer tumors and 105 chronic gastritis tissues were measured by quantitative real-time PCR. In the tumor specimens and the adjacent normal tissues EBV was found in 60% and 30.9%, CMV in 14% and 4.7%, and HHV-6 in 18%, and 14.2%, respectively. The detection rate of EBV and CMV was found to be significantly higher in tumor tissues relative to the adjacent normal tissues. Also, in chronic gastritis, the frequency of EBV, CMV, and HHV-6 was 19%, 12.3%, and 15.2%, respectively, compared with 16.4%, 1.1%, and 8.2% in their corresponding normal tissues. Here, the CMV frequency was found to be significantly higher in gastritis tissues relative to the adjacent normal tissues. Furthermore, viral load in both gastric cancer and gastritis groups was higher in either tumor or gastritis lesion compared with matched adjacent normal tissue. This study showed a clear association between gastric cancer with both EBV and CMV. Meanwhile, analyses revealed a strong association between the EBV, CMV, and HHV-6 viral loads with gastritis (P = 0.0026, P 0.0001, and P = 0.0405, respectively). Our results suggest that these three viruses might contribute to the induction and development the gastritis and gastric cancer.
- Published
- 2022
45. Expression of the human herpesvirus 6A latency-associated transcript U94A impairs cytoskeletal functions in human neural cells
- Author
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Jessica M. Hogestyn, Garrick Salois, Li Xie, Connor Apa, Justin Youngyunpipatkul, Christoph Pröschel, and Margot Mayer-Pröschel
- Subjects
Oligodendrocyte Precursor Cells ,Central Nervous System ,Cellular and Molecular Neuroscience ,Multiple Sclerosis ,Herpesvirus 6, Human ,Humans ,Cell Biology ,Molecular Biology ,Neuroglia ,Article - Abstract
Many neurodegenerative diseases have a multifactorial etiology and variable course of progression that cannot be explained by current models. Neurotropic viruses have long been suggested to play a role in these diseases, although their exact contributions remain unclear. Human herpesvirus 6A (HHV-6A) is one of the most common viruses detected in the adult brain, and has been clinically associated with multiple sclerosis (MS), and, more recently, Alzheimer's disease (AD). HHV-6A is a ubiquitous viral pathogen capable of infecting glia and neurons. Primary infection in childhood is followed by the induction of latency, characterized by expression of the U94A viral transcript in the absence of viral replication. Here we examine the effects of U94A on cells of the central nervous system. We found that U94A expression inhibits the migration and impairs cytoplasmic maturation of human oligodendrocyte precursor cells (OPCs) without affecting their viability, a phenotype that may contribute to the failure of remyelination seen in many patients with MS. A subsequent proteomics analysis of U94A expression OPCs revealed altered expression of genes involved in tubulin associated cytoskeletal regulation. As HHV-6A seems to significantly be associated with early AD pathology, we extended our initially analysis of the impact of U94A on human derived neurons. We found that U94A expression inhibits neurite outgrowth of primary human cortical neurons and impairs synapse maturation. Based on these data we suggest that U94A expression by latent HHV-6A in glial cells and neurons renders them susceptible to dysfunction and degeneration. Therefore, latent viral infections of the brain represent a unique pathological risk factor that may contribute to disease processes.
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- 2022
46. Biomarkers in the diagnostic algorithm of myalgic encephalomyelitis/chronic fatigue syndrome
- Author
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Sabine Gravelsina, Anda Vilmane, Simons Svirskis, Santa Rasa-Dzelzkaleja, Zaiga Nora-Krukle, Katrine Vecvagare, Angelika Krumina, Iana Leineman, Yehuda Shoenfeld, and Modra Murovska
- Subjects
Fatigue Syndrome, Chronic ,Adrenergic Agents ,Herpesvirus 6, Human ,Immunology ,Immunology and Allergy ,Humans ,DNA ,Receptors, Muscarinic ,Biomarkers ,Algorithms ,Autoantibodies ,Receptors, Adrenergic - Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease that is mainly diagnosed based on its clinical symptoms. Biomarkers that could facilitate the diagnosis of ME/CFS are not yet available; therefore, reliable and clinically useful disease indicators are of high importance. The aim of this work was to analyze the association between ME/CFS clinical course severity, presence of HHV-6A/B infection markers, and plasma levels of autoantibodies against adrenergic and muscarinic acetylcholine receptors. A total of 134 patients with ME/CFS and 33 healthy controls were analyzed for the presence of HHV-6A/B using PCRs, and antibodies against beta2-adrenergic receptors (β2AdR) and muscarinic acetylcholine receptors (M3 AChR and M4 AChR) using ELISAs. HHV-6A/B U3 genomic sequence in whole-blood DNA was detected in 19/31 patients with severe ME/CFS, in 18/73 moderate ME/CFS cases, and in 7/30 mild ME/CFS cases. Severity-related differences were found among those with a virus load of more than 1,000 copies/106 PBMCs. Although no disease severity-related differences in anti-β2AdR levels were observed in ME/CFS patients, the median concentration of these antibodies in plasma samples of ME/CFS patients was 1.4 ng/ml, while in healthy controls, it was 0.81 ng/ml, with a statistically significant increased level in those with ME/CFS (p = 0.0103). A significant difference of antibodies against M4 AChR median concentration was found between ME/CFS patients (8.15 ng/ml) and healthy controls (6.45 ng/ml) (p = 0.0250). The levels of anti-M4 plotted against disease severity did not show any difference; however, increased viral load correlates with the increase in anti-M4 level. ME/CFS patients with high HHV-6 load have a more severe course of the disease, thus confirming that the severity of the disease depends on the viral load—the course of the disease is more severe with a higher viral load. An increase in anti-M4 AchR and anti-β2AdR levels is detected in all ME/CFS patient groups in comparison to the control group not depending on ME/CFS clinical course severity. However, the increase in HHV-6 load correlates with the increase in anti-M4 level, and the increase in anti-M4 level, in turn, is associated with the increase in anti-β2AdR level. Elevated levels of antibodies against β2AdR and M4 receptors in ME/CFS patients support their usage as clinical biomarkers in the diagnostic algorithm of ME/CFS.
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- 2022
47. Herpesvirus and neurological manifestations in patients with severe coronavirus disease
- Author
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Vanessa Cristine de Souza, Carneiro, Soniza Vieira, Alves-Leon, Dmitry José de Santana, Sarmento, Wagner Luis da Costa Nunes Pimentel, Coelho, Otacilio da Cruz, Moreira, Andreza Lemos, Salvio, Carlos Henrique Ferreira, Ramos, Carlos Henrique Ferreira, Ramos Filho, Carla Augusta Barreto, Marques, João Paulo, da Costa Gonçalves, Luciane Almeida Amado, Leon, and Vanessa Salete, de Paula
- Subjects
Infectious Diseases ,SARS-CoV-2 ,Herpesvirus 6, Human ,Virology ,viruses ,COVID-19 ,Cytomegalovirus ,Humans ,virus diseases ,Herpesvirus 7, Human ,Herpesviridae Infections ,Herpesviridae - Abstract
Background Certain clinical manifestations of coronavirus disease (COVID-19) mimic those associated with human herpesvirus (HHV) infection. In this study, we estimated the prevalence of herpesvirus in patients with COVID-19 and determined if coinfection is associated with poorer outcomes and neurological symptoms. Methods We analyzed samples of 53 patients diagnosed with COVID-19. The samples were evaluated for the presence of alphaherpesviruses, betaherpesviruses, and gammaherpesviruses, and the viral loads were quantified using quantitative polymerase chain reaction (qPCR) method. Results Among the patients, in 79.2% had detection at least one type of herpesvirus. HHV-6 (47.2%), cytomegalovirus (43.3%), and HHV-7 (39.6%) showed the highest detection rates. Patients with a high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) load were more likely to show herpes simplex virus 1 detection (p = 0.037). Among patients coinfected with SARS-CoV-2 and HHVs, 26.4% showed central nervous system-associated neurological symptoms and herpetic manifestations. A statistically significant association was observed between neurological changes and HHV-6 detection (p = 0.034). Conclusions The findings showed a high prevalence of herpesvirus in patients with COVID-19. Furthermore, even though SARS-CoV-2 and HHV coinfection was not associated with poorer outcomes, the findings demonstrated the association between neurological symptoms and HHV-6 detection.
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- 2022
48. The role of early natural killer cell adoptive infusion before engraftment in protecting against human herpesvirus <scp>‐6B</scp> encephalitis after naïve <scp>T</scp> ‐cell‐depleted allogeneic stem cell transplantation
- Author
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Raquel Olivas-Mazón, Alba Fernández-Arroyo, Antonio Marcos, Ana Belén Romero, Victor Jiménez Yuste, Aida Constanzo, Antonio Balas, David Bueno, Cristina Ferreras, Mercedes Gasior, Jose L. Vicario, Antonio Pérez-Martínez, Berta González, Raquel de Paz, Yasmina Mozo, Isabel Mirones, Luisa Sisinni, Adela Escudero, and Juan Torres Canizales
- Subjects
Male ,Adolescent ,Naive T cell ,Herpesvirus 6, Human ,T-Lymphocytes ,medicine.medical_treatment ,Immunology ,Graft vs Host Disease ,Roseolovirus Infections ,chemical and pharmacologic phenomena ,Hematopoietic stem cell transplantation ,030204 cardiovascular system & hematology ,Lymphocyte Depletion ,Natural killer cell ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,immune system diseases ,medicine ,Humans ,Transplantation, Homologous ,Immunology and Allergy ,Child ,biology ,business.industry ,Hematopoietic Stem Cell Transplantation ,Infant ,Hematology ,medicine.disease ,biology.organism_classification ,Adoptive Transfer ,Killer Cells, Natural ,Transplantation ,surgical procedures, operative ,medicine.anatomical_structure ,Child, Preschool ,Encephalitis ,Female ,Human herpesvirus 6 ,Stem cell ,business ,030215 immunology - Abstract
Background Naive T-cell-depleted grafts have been employed as an ex vivo T-cell depletion (TCD) platform to prevent graft-versus-host disease (GvHD) and improve immune reconstitution by providing rapid donor memory T-cell reconstitution after allogenic hematopoietic stem cell transplantation (allo-HSCT). CD45RA- memory T cells confer protection against viruses such as cytomegalovirus, Epstein-Barr virus, and adenovirus; however, reports have shown an unexpectedly high incidence of human herpesvirus (HHV)-6B encephalitis among pediatric allo-HSCT patients. Methods We report the first 18 consecutive allo-HSCT, 16 haplo-HSCT, and two human leukocyte antigen-matched related donors implanted with naive TCD grafts. All donors were administered three cell products: first, a CD34+ stem cell product; second, a CD45RA+ TCD graft, followed by an adoptive natural killer (NK) cell infusion within 10 days after HSCT. The study's primary endpoint was the incidence of HHV-6B encephalitis. Results Engraftment was achieved in 94.5% of cases; 2-year overall survival, event-free survival, and GvHD/relapse-free survival were 87.2% (95% CI 78.6-95.8), 67.3% (95% CI 53.1-81.5), and 64% (95% CI 50.5-78.1), respectively. HHV-6B reactivation occurred in 7 of the haplo-HSCT patients, six of who received a cell infusion with an NK/CD4 ratio Conclusions In this clinical study, we show that early adoptive NK cell infusion after a 45RA+ TCD allo-HSCT graft is safe and can prevent HHV-6B encephalitis. We recommend infusing adoptive NK cells after allo-HSCT using CD45RA+ TCD grafts.
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- 2021
49. IRAK4 Deficiency Presenting with Anti-NMDAR Encephalitis and HHV6 Reactivation
- Author
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Osamu Ohara, Hidetoshi Takada, Vanessa Sancho-Shimizu, Kunihiko Moriya, Capucine Picard, Shiho Nishimura, Sarosh R. Irani, Hidenori Ohnishi, Zenichiro Kato, Masao Kobayashi, Jean-Laurent Casanova, Nobutsune Ishikawa, Miyuki Tsumura, Satoshi Okada, Yoko Mizoguchi, Anne Puel, Sonoko Sakata, Yoshiyuki Kobayashi, and Medical Research Council (MRC)
- Subjects
Male ,0301 basic medicine ,anti-NMDAR encephalitis ,Herpesvirus 6, Human ,DNA Mutational Analysis ,Mutant ,medicine.disease_cause ,Compound heterozygosity ,BACTERIAL-INFECTIONS ,Autoimmunity ,ACTIVATION ,0302 clinical medicine ,Genes, Reporter ,Immunology and Allergy ,Medicine ,INTERLEUKIN-1 ,HHV6 ,Receptor ,Anti-N-Methyl-D-Aspartate Receptor Encephalitis ,autoimmunity ,Brain ,Disease Management ,IRAK4 ,Magnetic Resonance Imaging ,Pedigree ,D-ASPARTATE RECEPTOR ,Interleukin-1 Receptor-Associated Kinases ,1107 Immunology ,Original Article ,Disease Susceptibility ,Symptom Assessment ,Life Sciences & Biomedicine ,Encephalitis ,Primary Immunodeficiency Diseases ,Immunology ,Roseolovirus Infections ,DIAGNOSIS ,Diagnosis, Differential ,03 medical and health sciences ,2 SIBLINGS ,Immunity ,Humans ,Genetic Predisposition to Disease ,Allele ,Alleles ,Science & Technology ,business.industry ,MUTATIONS ,Infant ,PATHWAYS ,medicine.disease ,HEK293 Cells ,030104 developmental biology ,Mutation ,ANTIBODIES ,Virus Activation ,MYD88 ,business ,Biomarkers ,030217 neurology & neurosurgery - Abstract
IRAK4 deficiency is an inborn error of immunity predisposing patients to invasive pyogenic infections. Currently, there is no established simple assay that enables precise characterization of IRAK4 mutant alleles in isolation. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune condition that is characterized by psychiatric symptoms, involuntary movement, seizures, autonomic dysfunction, and central hypoventilation. It typically occurs in adult females associated with tumors. Only a few infantile cases with anti-NMDAR encephalitis have been so far reported. We identified a 10-month-old boy with IRAK4 deficiency presenting with anti-NMDAR encephalitis and human herpes virus 6 (HHV6) reactivation. The diagnosis of IRAK4 deficiency was confirmed by the identification of compound heterozygous mutations c.29_30delAT (p.Y10Cfs*9) and c.35G>C (p.R12P) in the IRAK4 gene, low levels of IRAK4 protein expression in peripheral blood, and defective fibroblastic cell responses to TLR and IL-1 (TIR) agonist. We established a novel NF-κB reporter assay using IRAK4-null HEK293T, which enabled the precise evaluation of IRAK4 mutations. Using this system, we confirmed that both novel mutations identified in the patient are deleterious. Our study provides a new simple and reliable method to analyze IRAK4 mutant alleles. It also suggests the possible link between inborn errors of immunity and early onset anti-NMDAR encephalitis. Electronic supplementary material The online version of this article (10.1007/s10875-020-00885-5) contains supplementary material, which is available to authorized users.
- Published
- 2021
50. In silico assessment of binding affinities of three dementia-protective Human Leukocyte Antigen (HLA) alleles to nine human herpes virus antigens
- Author
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Spyros Charonis, Lisa M. James, and Apostolos P. Georgopoulos
- Subjects
0301 basic medicine ,Herpesvirus 6, Human ,viruses ,In silico ,Human leukocyte antigen ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Epitope ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Antigen ,HLA Antigens ,Humans ,Computer Simulation ,Allele ,Receptor ,Antigens, Viral ,Alleles ,chemistry.chemical_classification ,General Medicine ,Virology ,Amino acid ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Dementia ,HLA-DRB1 Chains - Abstract
Background Human herpes viruses (HHV) have been implicated in dementia. Class II Human Leukocyte Antigens (HLA) play a critical role in host protection from foreign antigens including herpes viruses through stimulating antibody production against them. In the present study we investigated the in silico binding affinity of 9 H HV to three Class II HLA alleles that have been found to protect against dementia: DRB1*01:01, DRB1*13:02, and DRB1*15:01. Methods A sliding window approach was used to partition the amino acid sequences of surface glycoproteins from HHV 1–8 into subsequences. The binding affinity of the HHV subsequences to Class II HLA surface receptor proteins was predicted using the Sturniolo method in the Immune Epitope Database and reported as a percentile rank. The binding affinity of HHV subsequences to protective alleles was compared to that of three dementia-neutral Class II HLA alleles: DRB1*03:01, DRB1*07:01, and DRB1*08:01. Findings Binding affinity varied widely for each HLA allele, HHV type, and HHV subsequence. The protective alleles had significantly higher binding affinity that than the neutral alleles. The largest differences in binding affinity between the protective and neutral alleles was shown for HHV-6A and HHV-6B, which had the best overall binding affinity with the protective alleles. Interpretation The dementia protection conferred by the three protective HLA alleles investigated here is related to their superior ability to bind and successfully eliminate HHV epitopes – in particular, HHV6 - that could otherwise cause dementia if they persisted.
- Published
- 2020
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