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Xun Zhou,1,2,* Jingzhou Liu,2,* Shuang Xiao,2,3,* Xiaoqing Liang,1,2 Yi Li,2 Fengzhen Mo,3 Xin Xin,2 Yang Yang,2 Chunsheng Gao1,2 1School of Pharmacy, Henan University, Kaifeng, People’s Republic of China; 2State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, People’s Republic of China; 3School of Pharmacy, Guangxi Medical University, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fengzhen Mo; Xin Xin, Email mofzhen@163.com; 13511014091@163.comAbstract: Gene therapy aims to add, replace or turn off genes to help treat disease. To date, the US Food and Drug Administration (FDA) has approved 14 gene therapy products. With the increasing interest in gene therapy, feasible gene delivery vectors are necessary for inserting new genes into cells. There are different kinds of gene delivery vectors including viral vectors like lentivirus, adenovirus, retrovirus, adeno-associated virus et al, and non-viral vectors like naked DNA, lipid vectors, polymer nanoparticles, exosomes et al, with viruses being the most commonly used. Among them, the most concerned vector is adeno-associated virus (AAV) because of its safety, natural ability to efficiently deliver gene into cells and sustained transgene expression in multiple tissues. In addition, the AAV genome can be engineered to generate recombinant AAV (rAAV) containing transgene sequences of interest and has been proven to be a safe gene vector. Recently, rAAV vectors have been approved for the treatment of various rare diseases. Despite these approvals, some major limitations of rAAV remain, namely nonspecific tissue targeting and host immune response. Additional problems include neutralizing antibodies that block transgene delivery, a finite transgene packaging capacity, high viral titer used for per dose and high cost. To deal with these challenges, several techniques have been developed. Based on differences in engineering methods, this review proposes three strategies: gene engineering-based capsid modification (capsid modification), capsid surface tethering through chemical conjugation (surface tethering), and other formulations loaded with AAV (virus load). In addition, the major advantages and limitations encountered in rAAV engineering strategies are summarized.Keywords: AAV engineering, capsid modification, surface tethering, virus load, rational design, directed evolution, machine learning

Copyright of Farmacia is the property of Societatea de Stiinte Farmaceutice Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cytomegalovirus (CMV) infection is the most common opportunistic infection that occurs following orthotopic liver transplantation (OLT). In addition to the direct infection-related symptoms, it also triggers an immunological response that may contribute to adverse clinical outcomes. CMV disease has been described as a predictor of invasive fungal infections (IFIs) but its role under an antiviral prophylaxis regimen is unclear. Methods: We retrospectively analyzed the medical records of 214 adult liver transplant recipients (LTRs). Universal antiviral prophylaxis was utilized in recipients with CMV mismatch; intermediate- and low-risk patients received pre-emptive treatment. Results: Six percent of patients developed CMV disease independent of their serostatus. The occurrence of CMV disease was associated with elevated virus load and increased incidence of leucopenia and IFIs. Furthermore, CMV disease was associated with higher one-year mortality and increased relapse rates within the first year of OLT. Conclusions: CMV disease causes significant morbidity and mortality in LTRs, directly affecting transplant outcomes. Due to the increased risk of IFIs, antifungal prophylaxis for CMV disease may be appropriate. Postoperative CMV monitoring should be considered after massive transfusion, even in low-risk serostatus constellations. In case of biliary complications, biliary CMV monitoring may be appropriate in the case of CMV-DNA blood-negative patients. [ABSTRACT FROM AUTHOR]

Aim: Human bocavirus 1 (HBoV1) has been associated with respiratory tract infections in children. We aimed at retrospectively describing patient characteristics, seasonality, pre‐existing medical conditions, codetections, clinical manifestations and complications of HBoV1 infection in relation to viral load in the child population in Stockholm, with the overarching aim of elucidating the clinical significance of HBoV1. Methods: We included all hospitalised children 0—17 years testing positive for HBoV1 by real‐time polymerase chain reaction on nasopharyngeal aspirates 1 July 2008—30 June 2019. Patients with HBoV1 single detection, high viral load expressed as an HBoV1‐DNA cycle threshold (Ct) < 25, or both, were separately analysed. We retrieved information on pre‐existing conditions and clinical course from the medical records. Results: We found 768 episodes in 727 children, 496 (64.6%) male and 441 (60.7%) previously healthy. The median age was 17.6 months. Most (476/768, 62.0%) episodes occurred during December–March. HBoV1 was in 549 episodes (71.5%) codetected with other viruses. Ct < 25 was independently associated with young age, single detection of HBoV1 and presentation early in the epidemic season. We saw few differences in clinical manifestations between the subgroups. Conclusion: Our findings are consistent with primary HBoV1 infection causing mild‐to‐severe respiratory tract manifestations in young children. [ABSTRACT FROM AUTHOR]

Background: H1N1 influenza viruses are the leading cause of severe respiratory virus infections worldwide. Resistance to the current selections of anti-influenza agents are still of concern. The Zingiber officinale root is one of the most heavily consumed dietary substances. It is also been traditionally used against common cold in Ayurveda and Chinese herbal medicine. Purpose: Investigation on in vitro and in vivo effect of [6]-gingerol from Zingiber officinale against influenza virus infection. Methods: In vitro antiviral property of [6]-gingerol was measured by the plaque reduction assay in which MDCK cells were infected with PR8 strain of H1N1 influenza A virus in the presence of gingerol. Gingerol-mediated inhibition of influenza neuraminidase activity was tested by MUNANA assay in vitro. In vivo activity was tested in PR8 strain of H1N1 influenza virus infected mice. Modulation of anti-influenza immunity was tested by the study of hemagglutinin-specific T cells in vivo. Results: [6]-Gingerol significantly reduced in vitro infection by PR8 strain of H1N1 influenza virus, with an IC50 value 2.25±0.18 μM. The inhibition was associated with the inhibition of viral neuraminidase activity, over 75% of the NA enzymatic activity of 2.5 × 103 PFUs of PR8 strain influenza virus at a concentration of 2 μM. Oseltamivir (Tamiflu) served as a positive control, which inhibited the NA enzymatic activity with an IC50 value of 1.88±0.05 μM. In H1N1 influenza virus infected mice, gingerol treatment (oral, once daily for 5 days) reduced virus load in the lungs and attenuated body weight loss and mortality. Gingerol inhibited viral neuraminidase-mediated intracellular TGF-β activation of lung-infiltrating CD4+ T cells. With the constrained active-TGF-β and immune suppression, influenza hemagglutinin-specific Th1 and Th17 immunity was increased. Conclusion: [6]-Gingerol from Z. officinale is a potent anti-influenza compound that inhibits viral neuraminidase activity and boosts hemagglutinin-specific CD4+ T cell response to the infection. Taken together, gingerol has the potential to be further evaluated for clinical applications in human influenza.

Introduction: The control of Newcastle disease virus (NDV) infection depends solely on vaccination which in most cases is not sufficient to restrain the consequences of such a highly evolving viral disease. Finding out substances for preparing an efficient anti-ND drug would be of high value. n-Docosanol is a saturated fatty alcohol with an inhibitory effect against many enveloped viruses. In this study, we evaluated the therapeutic effect of n-docosanol on NDV infection and shedding in chickens. Methods: Chickens infected with a highly virulent NDV were treated with low to high concentrations of n-docosanol (20, 40, and 60 mg/kg body weight) for 4-successive days, once they showed the disease symptoms. Survival and curative rates, virus load, histopathological scoring, and virus shedding were defined. Results: Symptoms development was found to discontinue 24–72 hours post-treatment. Survival rate in the NDV-infected chickens raised 37.4–53.2% after the treatment. n-Docosanol treatment was also found to significantly reduce virus load in the digestive (26.2–33.9%), respiratory (38.3–63%), nervous (26.7–51.1%), and lymphatic (16.4–29.1%) tissues. Histopathological scoring of NDV lesions revealed prominent rescue effects on the histology of different tissues. Importantly, n-docosanol treatment significantly reduced virus shedding in oropharyngeal discharge and feces thereby allowing the restriction of NDV spread. Conclusion: Our findings suggest n-docosanol as a promising remedy in the control strategy of Newcastle disease in the poultry industry. [ABSTRACT FROM AUTHOR]

IntroductionThe control of Newcastle disease virus (NDV) infection depends solely on vaccination which in most cases is not sufficient to restrain the consequences of such a highly evolving viral disease. Finding out substances for preparing an efficient anti-ND drug would be of high value. n-Docosanol is a saturated fatty alcohol with an inhibitory effect against many enveloped viruses. In this study, we evaluated the therapeutic effect of n-docosanol on NDV infection and shedding in chickens.MethodsChickens infected with a highly virulent NDV were treated with low to high concentrations of n-docosanol (20, 40, and 60 mg/kg body weight) for 4-successive days, once they showed the disease symptoms. Survival and curative rates, virus load, histopathological scoring, and virus shedding were defined.ResultsSymptoms development was found to discontinue 24–72 hours post-treatment. Survival rate in the NDV-infected chickens raised 37.4–53.2% after the treatment. n-Docosanol treatment was also found to significantly reduce virus load in the digestive (26.2–33.9%), respiratory (38.3–63%), nervous (26.7–51.1%), and lymphatic (16.4–29.1%) tissues. Histopathological scoring of NDV lesions revealed prominent rescue effects on the histology of different tissues. Importantly, n-docosanol treatment significantly reduced virus shedding in oropharyngeal discharge and feces thereby allowing the restriction of NDV spread.ConclusionOur findings suggest n-docosanol as a promising remedy in the control strategy of Newcastle disease in the poultry industry.

Background: Coronavirus disease 2019 (COVID‐19) is a new pandemic disease, associated with substantial morbidity and mortality. Its diagnosis requires centralized facilities and time. Aims: To describe the exposure history and clinical picture of the COVID‐19 patients, to study the SARS‐CoV‐2 Virus load and some determinants that may correlate with its prognosis, and to evaluate the role of inflammatory index NLR as an early predictor of COVID‐19 prognosis. Methodology: A prospective follow‐up study included laboratory‐confirmed 179 COVID‐19 cases out of 660 suspected COVID‐19 cases, at El‐Madinah El‐Monawarah General Hospital in April 2020. Confirmed cases were managed by the Saudi Protocol and followed up every 2 weeks by PCR, neutrophil to lymphocyte ratio (NLR) for 1 month. Data were collected through a validated questionnaire and by qualified infection control staff. Results: The majority of the COVID‐19 cases were 67 (37.4%) aged 30 to <45 years, 157 (87.7%) males, 76.0% working outside the medical field. 38.0% were asymptomatic and 26.3% had severe symptoms, while the main presenting symptoms were fever and dry cough (49.7% and 43.6%), respectively. The case fatality was 7.8%. The male, nonmedical occupation, and low level of education had a statistically significant relationship with the baseline PCR. There was an inverse significant correlation between baseline PCR readings and the recovery duration and health status outcomes. NLR was noted to be significantly higher among old age, illiterate nonmedical occupation, case with severe symptoms, MICU admission, and worst health status outcomes, but it was paradoxically higher among nonadmitted positive cases. Conclusion: Admitted COVID‐19 cases outcomes (disease severity, ICU admission, and mortality) significantly correlated to NLR and not to the baseline PCR viral load. NLR could be a beneficial prognostic and triaging parameter especially old nonmedical COVID‐19 patients. [ABSTRACT FROM AUTHOR]

Posttransplant lymphoproliferative disease (PTLD) is a series of heterogeneous lymphoproliferative diseases and a severe complication af ter solid organ transplantation in children. Over 70% of PTLD is associated with Epstein-Barr virus (EBV). EBY-related B-cell lymphoma is also the main malignant tumor after pediatric organ transplantation. EBY-related PTLD is still a challenge in pediatric solid organ transplantation, which is mainly caused by immune function damage induced by immune suppression after transplantation. However, the specific mechanism remains elusive. In recent years, biomarkers have been developed to guide the diagnosis and individualized treatment of EBVrelated PTLD, which possesses excellent application prospect. In this article, research progresses on the incidence of EBVrelated PTLD in solid organ transplantation and its biomarkers were reviewed, aiming to explore novel ideas for clinical diagnosis and treatment. [ABSTRACT FROM AUTHOR]

A clinical case of hepatocirrhosis with chronic hepatitis C termination (1b genotype) is described. Taking into account the cirrhotic stage of the disease, the extrahepatic HCV replication in the peripheral mononuclears, unfavourable HCV genotype, infavourable IL-28B gene polymorphism, inefficiency of the previous two courses of the standard antiviral therapy (PegIFN + ribavirin) and secondary immune deficiency, noninterferon antiviral therapy for 24 weeks was used in the treatment of the patient: interferon-inductive therapy with cycloferon in combination with ribavirin. There was observed by the 12th week of the treatment biochemical remission and a significant decrease of the virus load from 1X107 IU/ml to 7X105 IU/ml in the blood serum and from 1.35X107 IU/ml to 8X105 IU/ml in the peripheral mononuclears. Investigation of the molecular biological markers of the viremia (PCR HCV-RNA) in the cells of peripheral mononuclears is an obligatory diagnostic technology in cases with suspected extra-hepatic HCV infection. The kinetics of the virus load and the positive dynamics of the immunological indices in the patient at the cirrhotic stage of chronic virus hepatitis C are indicative of the efficient etiopathogenic approach with the use of the noninterferon treatment scheme (cycloferon + ribavirin), when recombinant interferons are contraindicated.

Abstract Background Coronavirus disease 2019 (COVID‐19) is a new pandemic disease, associated with substantial morbidity and mortality. Its diagnosis requires centralized facilities and time. Aims To describe the exposure history and clinical picture of the COVID‐19 patients, to study the SARS‐CoV‐2 Virus load and some determinants that may correlate with its prognosis, and to evaluate the role of inflammatory index NLR as an early predictor of COVID‐19 prognosis. Methodology A prospective follow‐up study included laboratory‐confirmed 179 COVID‐19 cases out of 660 suspected COVID‐19 cases, at El‐Madinah El‐Monawarah General Hospital in April 2020. Confirmed cases were managed by the Saudi Protocol and followed up every 2 weeks by PCR, neutrophil to lymphocyte ratio (NLR) for 1 month. Data were collected through a validated questionnaire and by qualified infection control staff. Results The majority of the COVID‐19 cases were 67 (37.4%) aged 30 to

Potato apical leaf curl disease (PALCD) caused by ToLCNDV has emerged as a serious threat to potato cultivation in India. Host resistance to the virus is the potent strategy to curb the menace of this disease. Identification of potato germplasm free from ToLCNDV is a major challenge for healthy seed production and also for an effective resistance breeding programme. Novel and simple agro-inoculation of ToLCNDV was done to select resistant genotypes of potatoes. A set of 9 advanced hybrids and 4 control varieties were evaluated for resistance to ToLCNDV under controlled conditions at ICAR-Central Potato Research Institute, Shimla. Clear symptoms were visible in susceptible genotypes within 30 days after the first inoculation. Based on symptoms of the disease, a scale (0-5) was developed for ToLCNDV resistance screening. Phenotyping results showed the resistant reaction of SM/00-42, SM/00-120 and VMT5-1 to ToLCNDV. However, virus load quantification of inoculated plant samples revealed low virus load in LBY 18, VMT5-1 and SM/00-42. All the four control varieties showed moderately susceptible to susceptible reaction with Kufri Pukhraj showing the highest virus load among all genotypes. The hybrid, SM/00-42 was found to promising due to its resistant reaction and very low virus load. This can be effectively utilized in ToLCNDV resistance breeding or direct deployment after agronomic evaluation. Moreover, the scale developed in the present study could be used in preliminary screening for the disease. [ABSTRACT FROM AUTHOR]

Porcine circovirus type 3 (PCV3) is a newly described circovirus that has been identified in pig populations across the globe. The virus is associated with multiple diseases including reproductive and systemic diseases. As effective vaccines are lacking, surveillance is crucial for PCV3 control, but there are currently, few side-by-side comparisons of the efficacy of different samples for the detection of PCV3. This study collected four sample types, including colostrum, udder skin wipes, placental umbilical cord blood, and processing fluid from 134 litters in a sow farm from July to September 2021 for PCV3 detection based on quantitative PCR tests. Udder skin wipes showed the highest detection rates (76.9%), while 71.6% of the processing fluid, 49.3% of the placental umbilical cord, and 29.1% of the colostrum samples were positive. Logistic regression analysis suggested that the detection rates of udder skin wipes and processing fluid were similar (odds ratio for processing fluid vs udder skin wipes was 0.76, 95% confidence interval (CI) 0.43–1.32), but the two tests were probably not identifying the same population as infected, as the agreement between the samples was only moderate (Gwet's AC1: 0.65). In this study, we were able to demonstrate that PCV3 was present in the farrowing room throughout the period from birth to weaning using udder skin wipes, although viral load decreased over time. The odds of PCV3 detection in colostrum from 2-parity sows was three times higher (95% CI 1.4–6.8) than that of primiparous sows, while the odds of PCV3 detection in sows with mummified fetuses was 2.7 times higher (95% CI 1.1–6.6) than sows with no mummified fetuses. In conclusion, these results indicate that udder skin wipes have high detection rates in infected animals over the whole period from birth to weaning and would thus be suitable samples for PCV3 surveillance in the farrowing rooms. [ABSTRACT FROM AUTHOR]

Although Ma Huang Tang (MHT) has long been considered as a classical formula for respiratory infections like influenza, bronchitis and asthma, its chemical ingredients that really exert the main efficacy are still obscure. In this study we aimed to screen its antiviral components and investigate the potential mechanisms. The MDCK cellular research results showed that, among nine predominant ingredients of MHT, L-methylephedrin (LMEP), L-ephedrine (LEP) and D-pseudo- ephedrine (DPEP) significantly inhibited the proliferation of influenza A virus in vitro, and the inhibitory effect at 24 h after the treatment was more obvious than that at 48 h. They also significantly inhibited the mRNA expression levels of related genes in the TLR3, TLR4 and TLR7 signaling pathways, which were accompanied with the down-regulation of TNF-α level and the up-regulation of IFN-β level in the cell supernatant. Therefore, three Ephedra alkaloids exert an antiviral effect in vitro which may be closely related to the inhibition of viral replication and the modulation of inflammatory response. Animal research further indicated, at the 3rd and 7th days after infection, LEP and DPEP significantly attenuated lung injury, decreased lung index, virus load in the lung and the level of IL-1β in serum, inhibited the mRNA expression levels of TNF-α, TLR3, TLR4, TLR7, MyD88, NF-κB p65 and RIG-1 as well as the protein expression levels of TLR4, TLR7, MyD88 and NF-κB p65 and markedly increased thymus index, the level of IL-10 in serum and the mRNA expression level of IFN-γ. LEP and DPEP have certain protective effects on the influenza virus-infected mice, which may be associated with their abilities of effectively alleviating lung injury, improving the immunologic function of infected mice and adjusting the host’s TLRs and RIG-1 pathways. The overall findings demonstrate that, as effective and inexpensive natural substances, Ephedra alkaloids and MHT may have potential utility in clinical management.

Although Ma Huang Tang (MHT) has long been considered as a classical formula for respiratory infections like influenza, bronchitis and asthma, its chemical ingredients that really exert the main efficacy are still obscure. In this study we aimed to screen its antiviral components and investigate the potential mechanisms. The MDCK cellular research results showed that, among nine predominant ingredients of MHT, L-methylephedrin (LMEP), L-ephedrine (LEP) and D-pseudo- ephedrine (DPEP) significantly inhibited the proliferation of influenza A virus in vitro , and the inhibitory effect at 24 h after the treatment was more obvious than that at 48 h. They also significantly inhibited the mRNA expression levels of related genes in the TLR3, TLR4 and TLR7 signaling pathways, which were accompanied with the down-regulation of TNF-α level and the up-regulation of IFN-β level in the cell supernatant. Therefore, three Ephedra alkaloids exert an antiviral effect in vitro which may be closely related to the inhibition of viral replication and the modulation of inflammatory response. Animal research further indicated, at the 3rd and 7th days after infection, LEP and DPEP significantly attenuated lung injury, decreased lung index, virus load in the lung and the level of IL-1β in serum, inhibited the mRNA expression levels of TNF-α, TLR3, TLR4, TLR7, MyD88, NF-κB p65 and RIG-1 as well as the protein expression levels of TLR4, TLR7, MyD88 and NF-κB p65 and markedly increased thymus index, the level of IL-10 in serum and the mRNA expression level of IFN-γ. LEP and DPEP have certain protective effects on the influenza virus-infected mice, which may be associated with their abilities of effectively alleviating lung injury, improving the immunologic function of infected mice and adjusting the host's TLRs and RIG-1 pathways. The overall findings demonstrate that, as effective and inexpensive natural substances, Ephedra alkaloids and MHT may have potential utility in clinical management. [ABSTRACT FROM AUTHOR]

Copyright of China Tropical Medicine is the property of China Tropical Medicine Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Cassava brown streak disease (CBSD) and cassava mosaic disease (CMD) are two viral diseases that cause severe yield losses in cassava of up to 100%, thereby persistently threatening food and income security in sub-Saharan Africa. For effective management of these diseases, there is a critical need to develop and deploy varieties with dual resistance to CBSD and CMD. In this study, we determined the response of advanced breeding lines to field infection by cassava brown streak viruses (CBSVs) and cassava mosaic begomoviruses (CMBs). This aim helped in identifying superior clones for downstream breeding. In total, 220 cassava clones, three in uniform yield trials (UYTs) and 217 in a crossing block trial (CBT), were evaluated for virus and disease resistance. Field data were collected on disease incidence and severity. To detect and quantify CBSVs, 448 and 128 leaf samples from CBSD symptomatic and symptomless plants were analyzed by reverse transcription PCR and real-time quantitative PCR, respectively. In addition, 93 leaf samples from CMD symptomatic plants in the CBT were analyzed by conventional PCR using CMB species-specific primers. In the CBT, 124 (57%) cassava clones did not express CMD symptoms. Of the affected plants, 44 (55%) had single African cassava mosaic virus infection. Single Cassava brown streak virus (CBSV) infections were more prevalent (81.6%) in CBT clones than single Ugandan cassava brown streak virus (UCBSV) infection (3.2%). Of the three advanced clones in the UYT, NAROCASS 1 and NAROCASS 2 had significantly lower (P < 0.05) CBSD severity, incidence, and CBSV load than MH04/0300. In the UYT, only 22% of samples tested had CBSVs, and all showed a negative result for CMBs. The low disease incidence, severity, and viral load associated with NAROCASS 1 and NAROCASS 2 is evidence of their tolerance to both CBSD and CMD. Therefore, these two cassava clones should be utilized in CBSD and CMD management in Uganda, including their utilization as progenitors in further virus resistance breeding. Highlights • Host plant resistance is essential for management of cassava mosaic disease (CMD) and cassava brown streak disease (CBSD). • Disease evaluation based on symptoms need to be augmented with molecular tools for better disease assessment. • Cassava brown streak virus is the most prevalent virus causing CBSD in Uganda. [ABSTRACT FROM AUTHOR]

Middle East respiratory syndrome coronavirus (MERS-CoV) causes a spectrum of illness. We evaluated whether cycle threshold (Ct) values (which are inversely related to virus load) were associated with clinical severity in patients from Saudi Arabia whose nasopharyngeal specimens tested positive for this virus by real-time reverse transcription PCR. Among 102 patients, median Ct of 31.0 for the upstream of the E gene target for 41 (40%) patients who died was significantly lower than the median of 33.0 for 61 survivors (p = 0.0087). In multivariable regression analyses, risk factors for death were age >60 years), underlying illness, and decreasing Ct for each 1-point decrease in Ct). Results were similar for a composite severe outcome (death and/or intensive care unit admission). More data are needed to determine whether modulation of virus load by therapeutic agents affects clinical outcomes.

Background: Maternally derived serum antibody and viral load are thought to influence disease severity in primary respiratory syncytial virus (RSV) infection. As part of the AsPIRES study of RSV pathogenesis, we correlated various serum antibody concentrations and viral load with disease severity.Methods: Serum neutralizing antibody titers and levels of immunoglobulin G (IgG) to RSV fusion protein (F), attachment proteins of RSV group A and B, the CX3C region of G, and nasal viral load were measured in 139 full-term previously healthy infants with primary RSV infection and correlated with illness severity.Results: Univariate analysis showed no relationship between measures of serum antibody and severity. However, a multivariate model adjusting for age at the time of infection found a significant 0.56 decrease in severity score for each 2-fold increase in antibody concentration to RSV F. The benefit of antibody was greatest in infants ≤ 2 months of age. Additionally, estimated antibody titer at birth was correlated with age at infection, suggesting that higher antibody titers delay infection. Viral load did not differ by illness severity.Conclusion: Our data support the concept of maternal immunization with an RSV vaccine during pregnancy as a strategy for reducing the burden of RSV infection in full-term healthy infants exposed to RSV during their first winter. [ABSTRACT FROM AUTHOR]

We determined levels of tick-borne encephalitis (TBE) virus (TBEV) RNA in serum samples obtained from 80 patients during the initial phase of TBE in Slovenia. For most samples, levels were within the range of 3-6 log10 copies RNA/mL. Levels were higher in female patients than in male patients, but we found no association between virus load and several laboratory and clinical parameters, including severity of TBE. However, a weak humoral immune response was associated with a more severe disease course, suggesting that inefficient clearance of virus results in a more serious illness. To determine whether a certain genetic lineage of TBEV had a higher virulence potential, we obtained 56 partial envelope protein gene sequences by directly sequencing reverse transcription PCR products from clinical samples of patients. This method provided a large set of patient-derived TBEV sequences. We observed no association between phylogenetic clades and virus load or disease severity. [ABSTRACT FROM AUTHOR]

The Schlei fjord in northern Germany is the recipient water of a comprehensive eel, Anguilla anguilla (L.), stocking programme. Since 2015, stocked eels become alizarin red S marked, but to date no control mechanism is implemented in this stock enhancement measure to prevent anthropogenic spreading of diseases. Consequentially, it was possible that farmed stocking cohorts of 2015 and 2016 (in total ca. 1040 kg) were subsequently tested positive for anguillid herpesvirus 1 (Ang HV 1). For this study, 100 eels [total length (TL) 24.3-72.9 cm, age ca. 1-6 years] were caught in 2016 and investigated with regard to Ang HV 1 infection, parasite load ( Anguillicoloides crassus) and body conditions. 68% of the eels were found to be virus positive while larger specimens were more often infected. In addition, a fitted generalized linear model (area under the curve = 0.741) demonstrated that an increase in individual TL is accompanied with an increased risk of clinically relevant virus loads. Anguillicoloides crassus turned out to be an important stressor for eels, because parasite and virus load revealed a significant positive correlation. The results of this study evidently show the urgent need of a disease containment strategy for eel stocking programmes. [ABSTRACT FROM AUTHOR]

Recently, a gammaherpesvirus was described in domestic cats (FcaGHV1). The goal of the present study was to investigate the presence of FcaGHV1 in Swiss domestic cats and analyze potential risk factors. Blood samples from 881 cats presented to veterinarians in all Swiss cantons and from 91 stray cats and neoplastic tissue samples from 17 cats with lymphoma were evaluated. FcaGHV1 was detected by real-time PCR targeting the glycoprotein B gene, followed by sequencing. Blood samples were also tested for feline hemoplasmas, feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV). The molecular prevalence of FcaGHV1 was 6.0% (95% confidence interval (CI), 4.5−7.8%) in cats presented to veterinarians and 5.5% (95% CI, 1.8−12.4%) in stray cats. FcaGHV1 PCR-positive cats originated from 19/26 Swiss cantons. Factors significantly associated with FcaGHV1 detection included male sex, age >3 years, nonpedigree status and co-infection with FIV and hemoplasmas. Moreover, FeLV viremia tended to be associated with FcaGHV1 detection. High FcaGHV1 blood loads were found more frequently in FeLV-viremic cats and less frequently in hemoplasma-infected cats than in uninfected cats. Clinical information was unavailable for most of the 881 cats, but leukemia, carcinoma and cardiomyopathy were reported in FcaGHV1-positive cats. None of the tissue samples from the 17 cats with lymphoma tested positive for FcaGHV1. Sequence analyses revealed homogeneity among the Swiss isolates and >99.7% identity to published FcaGHV1 sequences. In conclusion, FcaGHV1 is present in Switzerland with a similar prevalence in cats presented to veterinarians and in stray cats. The pathogenic potential of FcaGHV1 needs further evaluation.

Background Previous findings show that corticosteroid treatment during the first acute wheezing episode may reduce recurrent wheezing in children with high rhinovirus genome load at 12-month follow-up. Longer-term effects have not been investigated prospectively. Methods After PCR confirmation of rhinovirus from nasopharyngeal aspirate, 79 children with the first acute wheezing episode were randomized to receive orally prednisolone or placebo for 3 days. The initiation of asthma control medication before the age of 5 years was confirmed from medical record and/or from parental interview. The outcome was the time to initiation of regular asthma control medication. Interaction analysis examined rhinovirus genome load. Results Fifty-nine (75%) children completed the follow-up. Asthma control medication was initiated in 40 (68%) children at the median age of 20 months. Overall, prednisolone did not affect the time to initiation of asthma control medication when compared to placebo ( P=.99). Rhinovirus load modified the effect of prednisolone regarding the time to initiation of asthma control medication ( P-value for interaction=.04). In children with high rhinovirus load (>7000 copies/mL; n=23), the risk for initiation of medication was lower in the prednisolone group compared to the placebo group ( P=.05). In the placebo group, asthma medication was initiated to all children with high rhinovirus load (n=9) during the 14 months after the first wheezing episode. Conclusions Overall, prednisolone did not affect the time to initiation of asthma control medication when compared to placebo. However, prednisolone may be beneficial in first-time wheezing children whose episode was severe and associated with high rhinovirus load. (ClinicalTrials.gov, NCT00731575). [ABSTRACT FROM AUTHOR]

Objective To evaluate the effects of hepatitis B virus on liver function, liver fibrosis, and liver pathological staging at different immune stages. Methods We made a retrospective analysis of 657 patients with chronic hepatitis B diagnosed in the First Hospital of Lanzhou University. Their liver function parameters, liver fibrosis parameters, and hepatitis B virus load were measured by automatic biochemical analyzer, automatic gamma-radiation immunity analyzer, and quantitative PCR analyzer, respectively. Effects of hepatitis B virus on liver function, liver fibrosis in different immune stages were analyzed by variance analysis. Effects of hepatitis B virus on liver pathological staging at different immune stages were analyzed by linear trend chi square test analysis. Results In ALT normal chronic hepatitis B patients group, viral load had mild effects on liver function and liver fibrosis parameters. However, in ALT abnormal chronic hepatitis B patients group, viral load had a significant effect on liver function and liver fibrosis parameters, and the effect was most obvious in ALT≥double upper limit of normal group. The specific manifestation was that with viral load increasing, liver function parameters including ALT, AST, TBiL, DBiL, and IBiL increased, while TP and ALB decreased. Liver fibrosis parameters HA, LN, PcⅢ, and CIV all increased (P<0.05). In ALT normal chronic hepatitis B patients group, viral load had no relationship with liver pathological staging. However, in ALT abnormal chronic hepatitis B patients group, especially ALT≥double upper limit of normal group, viral load was significantly related to liver pathological staging. Conclusion The effects of hepatitis B virus on patients' liver function at different immune stages were different, thus providing evidence-based medicine support for clinical antiviral treatment. [ABSTRACT FROM AUTHOR]

Forty PRRS-negative, three week-old weaned pigs were randomized into two groups in separate rooms and inoculated with a modified live PRRS vaccine (Fostera ® PRRS) or control (PBS). Four weeks after vaccination pigs were rehoused in a single room and challenged intranasally and intramuscularly with virulent PRRSV strain NADC20. Timed serum samples were collected and titrated for PRRS virus and anti-PRRS virus antibodies. The study concluded when ≥80% of the pigs in the control group were determined to be virus negative (27 days post-challenge). Mean duration of viremia was significantly lower ( p = 0.0327) for vaccinated pigs compared to non-vaccinated pigs. A significant reduction ( p ≤ 0.0053) in mean post-challenge viremia titer was seen in vaccinates compared to non-vaccinates from days 8 through 22 post-challenge. At the individual pig level, no pigs in the vaccinated group had detectible PRRSV in serum at the end of the study (27 days post-challenge), while 15% of non-vaccinated pigs remained positive for virus. [ABSTRACT FROM AUTHOR]