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Summary: The human pegivirus type 1 (HPgV‐1)—as known as hepatitis G virus and GB virus C—is a common single‐stranded RNA flavivirus. Because few studies have demonstrated an association between HPgV‐1 infection and disease, screening for HPgV‐1 is not performed routinely. Nonetheless, a beneficial impact of HPgV‐1 infection on HIV disease progression has been reported in multiple studies. Given the burden of HIV in Asia and the complex interactions between viral co‐infections and the host, we provide a comprehensive overview of the existing data from Asia on HPgV‐1 infection, including the prevalence and circulating genotypes in all Asian countries with data reported. This review highlights the research conducted thus far and emphasizes the need for additional studies on HPgV‐1 across the Asian continent. [ABSTRACT FROM AUTHOR]

We compared the plasma viromes of HIV-infected subjects with low versus high CD4(+) T cell counts from the United States and Uganda by using deep sequencing and detected HIV, hepatitis C virus, hepatitis B virus, GB virus C, anellovirus, and human endogenous retrovirus (HERV) reads. An increase in the proportion of reads for anelloviruses, a family of highly prevalent and genetically diverse human viruses, was seen in subjects with AIDS from both countries. The proportion of endogenous human retrovirus reads was increased in AIDS subjects from Uganda but not the United States. Progression to AIDS is therefore associated with changes in the plasma concentration of commensal viruses.

BACKGROUND: GB virus type C (GBV-C) is transmitted by sexual or parenteral exposure and is prevalent among patients receiving blood products. GBV-C is associated with lower human immunodeficiency virus (HIV) RNA and better survival among HIV-infected patients. Open questions are the presence and the direction of any causal relationship between GBV-C infection and HIV disease markers in the context of highly active antiretroviral therapy (HAART). METHODS: We used a limited access database obtained from the National Heart, Lung, and Blood Institutes Viral Activation Transfusion Study (VATS), a randomized controlled trial of leukoreduced vs nonleukoreduced transfusions to HIV-infected transfusion-naive patients. Blood samples from 489 subjects were tested for GBV-C markers. Cox regression models and inverse probability of treatment weights were used to examine the association between GBV-C coinfection and mortality in the VATS cohort. RESULTS: We found a significant reduction in mortality among GBV-C coinfected VATS subjects, after adjusting for HAART status, HIV RNA level, and CD4 cell count at baseline. Acquisition of GBV-C RNA (n = 39) was associated with lower mortality in 294 subjects who were GBV-C negative at baseline, adjusting for baseline covariates (hazard ratio = 0.22, 95% confidence interval [CI]: .08-.58) and in models in which weights were used to control for time-updated covariates (odds ratio = 0.21, 95% CI: .08-.60). CONCLUSIONS: GBV-C viremia is associated with lower mortality, and GBV-C acquisition via transfusion is associated with a significant reduction in mortality in HIV-infected individuals, controlling for HIV disease markers. These findings provide the first evidence that incident GBV-C infection alters mortality in HIV-infected patients.

Human pegivirus (HPgV), previously called hepatitis G virus or GB virus C, is a lymphotropic virus with undefined pathology. Because many viruses from the family Flaviviridae, to which HPgV belongs, are neurotropic, we studied whether HPgV could infect the central nervous system. We tested serum and cerebrospinal fluid samples from 96 patients with a diagnosis of encephalitis for a variety of pathogens by molecular methods and serology; we also tested for autoantibodies against neuronal antigens. We found HPgV in serum and cerebrospinal fluid from 3 patients who had encephalitis of unclear origin; that is, all the markers that had been tested were negative. Single-strand confirmation polymorphism and next-generation sequencing analysis revealed differences between the serum and cerebrospinal fluid–derived viral sequences, which is compatible with the presence of a separate HPgV compartment in the central nervous system. It is unclear whether HPgV was directly responsible for encephalitis in these patients.

Background and objectives: The local prevalence of HPgV‐1 has been reported from different countries worldwide, but the global prevalence of HPgV‐1 remains unknown. The aim of this systematic review and meta‐analysis was to gather data from the literature to estimate the prevalence of HPgV‐1 in healthy volunteer blood donors in the world. Materials and methods: We searched PubMed, EMBASE, Scopus and Google Scholar databases for records up to January 2019 and included studies reporting HPgV‐1 virus prevalence amongst healthy volunteer blood donors based on the detection of HPgV‐1 RNA. Results: In all, we included 79 studies for the systematic review and 63 for the meta‐analysis. Based on the random effect meta‐analysis of 35 468 volunteer blood donors, we found the global prevalence of HPgV‐1 to be 3·1% (95% CI, 2·4–4·1). The pooled prevalences of HPgV‐1 were 1·7% (95% CI, 1·1–2·6) in North America, 9·1% (95% CI, 6·4–12·7) in South America, 2·3% (95% CI, 2%, 2·8) in Europe and 2·4% (95% CI, 1·4–4) in Asia. Subgroup analyses based on age, gender or risk factors were not possible. Conclusion: Approximately 3 in 100 blood donations worldwide are positive for HPgV‐1 increasing the risk of infection from transfusion of their components to subsequent recipients. Further research on virus pathogenicity is required before recommending routine screening of HPgV‐1 for healthy volunteer blood donors. [ABSTRACT FROM AUTHOR]

Background and Objectives: Red blood cell (RBC) transfusion is necessary for the prevention and treatment of a variety of life-threatening injuries and diseases. However, viral contamination of these products is a great threat to recipients. Screening donors for GB virus C by nucleic acid testing is not routinely implemented worldwide. The aim of the present study was to evaluate prevalence of GBV-C RNA in whole blood/red cell components. Methods: In this cross sectional pilot study, we collected 153 units of packed RBCs from blood banks of two public hospitals in Gorgan (northeast of Iran), between October and November 2014. The samples were screened for the presence of GBV-C RNA in plasma by nested RT-PCR using specific primers targeting highly conserved regions of 5' UTR of GBV-C. Data were analyzed using SPSS software (version 18). Results: Overall, 48 (31.37%) whole blood or red cell components were positive for GBV-C viremia. The GBV-C RNA was detected in 31/88 citrate phosphate dextrose-adenine 1 (CPDA1) RBC, 16/50 washed RBC and 1/13 reduced-leukocyte RBC. However, whole blood CPDA1 was negative for GBV-C viremia. Direct sequencing of PCR products confirmed GBV-C contamination. Conclusions: Transmission of GBV-C infection was observed in blood products. Thus, efforts should be made to develop new strategies for assuring blood transfusion safety. [ABSTRACT FROM AUTHOR]

Highly active antiretroviral therapy has revolutionized the battle against human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). From its current global rollout, HIV/AIDS morbidity and mortality has been greatly reduced, yet there exists substantial interest in the development of new therapies to further mitigate the HIV/AIDS health burden and to inhibit any fallout from the development of antiretroviral drug resistance. One potential intervention is the human pegivirus (HPgV). HPgV is not known to cause disease, and most remarkably it is shown to delay the progression of HIV to AIDS. However, the health benefit of increasing HPgV prevalence in the community of HIV-infected men remains unknown at the public health level. We evaluated the utility of HPgV biovaccination for mitigating the HIV/AIDS health burden using mathematical models. Importantly, our work considers the potential concern that HPgV will, itself, evolve to become disease-causing by permitting mutant disease-causing HPgV strains to potentially arise during treatment. Our findings show that HPgV biovaccination rates of 12.5%–50% annually could prevent 4.2–23.6 AIDS incidences and 3.3–18.8 AIDS deaths, and could save 2.9–18.6 disability-adjusted life years per 1,000 people. Together, these findings indicate that HPgV biovaccination could be an effective therapy for reducing HIV/AIDS morbidity and mortality, and thus warrants further exploration. [ABSTRACT FROM AUTHOR]

Anelloviridae and Human Pegivirus 1 (HPgV-1) blood burden have been postulated to behave as surrogate markers for immunosuppression in transplant recipients. Here, we assessed the potential utility plasma Torque teno virus (TTV), total Anelloviridae (TAV), and HPgV-1 load monitoring for the identification of allogeneic hematopoietic stem cell transplantation recipients (allo-HSCT) at increased risk of infectious events or acute graft versus host disease (aGvHD). In this single-center, observational study, plasma TTV DNA, TAV DNA, and HPgV-1 RNA loads were monitored in 75 nonconsecutive allo-HSCT recipients (median age, 54 years). Monitoring was conducted before at baseline or by days +30, +60, +90, +120, and +180 after transplantation. Pneumonia due to different viruses or Pneumocystis jirovecii, BK polyomavirus-associated haemorrhagic cystitis (BKPyV-HC), and Cytomegalovirus DNAemia were the infectious events considered in the current study. Kinetics of plasma TTV, TAV DNA, and HPgV-1 RNA load was comparable, with though and peak levels measured by days +30 and day +90 (+120 for HPgV-1). Forty patients (53%) developed one or more infectious events during the first 180 days after allo-HSCT, whereas 29 patients (39%) had aGvHD (grade II-IV in 18). Neither, TTV, TAV, nor HPgV-1 loads were predictive of overall infection or CMV DNAemia. A TTV DNA load cut-off ≥4.40 log 10 (pretransplant) and ≥4.58 log 10 (baseline) copies/mL predicted the occurrence of BKPyV-HC (sensitivity ≥89%, negative predictive value, ≥96%). TTV DNA loads ≥3.38 log 10 by day +30 anticipated the occurrence of aGvHD (sensitivity, 90%; negative predictive value, 97%). Pretransplant HPgV-1 loads were significantly lower (p = 0.03) in patients who had aGvHD than in those who did not. Monitoring of TTV DNA or HPgV-1 RNA plasma levels either before or early after transplantation may be ancillary to identify allo-HSCT recipients at increased risk of BKPyV-HC or aGvHD., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Objective: To determine the prevalence of human pegivirus (HPgV) and factors associated with vertical transmission among pregnant women infected with HIV.Method: A retrospective cross-sectional study was conducted among pregnant women treated at an HIV reference service in Rio Grande, Brazil, between January 1, 2010, and January 1, 2015. The polymerase chain reaction was used to diagnose HPgV infection among the women and their neonates. Clinical, obstetric, and neonatal data were obtained from medical records.Results: Infection with HPgV was detected among 16 (25%) of 63 women and 5 (8%) of 63 newborns, corresponding to a vertical transmission rate of 31%. Multivariate analysis demonstrated that the absence of prenatal care was the only risk factor for vertical transmission of HPgV (prevalence ratio 19.61, 95% confidence interval 1.29-297.48; P=0.032).Conclusion: Prenatal care could protect against vertical transmission of HPgV among women infected with HIV; however, studies among HIV-negative individuals are still required to verify this correlation. [ABSTRACT FROM AUTHOR]

Patients undergoing hemodialysis are at increased risk of infection with blood-borne viruses, including GB virus C (GBV-C) and torque teno virus (TTV). However, the prevalence and genotypic distribution of these viruses in the assessed patients undergoing hemodialysis remains unclear. The present study investigated these issues and the possibility of nosocomial transmission among patients undergoing hemodialysis in a unit in Yogyakarta, Indonesia. GBV-C RNA was detected in 92/161 patients (57.1%) by nested reverse-transcription polymerase chain reaction. Phylogenetic analysis of the 5'-untranslated region (UTR) classified the GBV-C isolates into genotypes 6 (85%), 2 (8%), 4 (6%), and 3 (1%). TTV DNA was detected in all patients by the amplification of the 5'-UTR and open reading frame-1 (ORF1) by nested and semi-nested polymerase chain reaction. Phylogenetic analysis based on the ORF1 revealed that genotype 1 was dominant (84%), followed by genotypes 2 (10%) and 3 (6%). The greater prevalence of GBV-C genotype 6 in patients undergoing hemodialysis compared with the general population and the identical sequences observed in multiple isolates provided strong evidence of patient-to-patient transmission. The prevalence of TTV in hemodialysis patients was similar to that observed in the general population, and only one pair of TTV isolates was identical. These results indicated that nosocomial infection was not the main cause of the high prevalence of TTV in patients undergoing hemodialysis. In conclusion, GBV-C and TTV infections are common in patients undergoing hemodialysis in Yogyakarta, Indonesia, and transmission is likely to be nosocomial in the case of GBV-C infection. [ABSTRACT FROM AUTHOR]

Background: Pseudorabies (PR) (also called Aujeszky's disease, AD) is a serious infectious disease affecting pigs and other animals worldwide. The emergence of variant strains of pseudorabies virus (PRV) since 2011 has led to PR outbreaks in China and a vaccine that antigenically more closely matches these PRV variants could represent an added value to control these infections., Methods: The objective of this study was to develop new live attenuated and subunit vaccines against PRV variant strains. Genomic alterations of vaccine strains were based on the highly virulent SD-2017 mutant strain and gene-deleted strains SD-2017ΔgE/gI and SD-2017ΔgE/gI/TK, which constructed using homologous recombination technology. PRV gB-DCpep (Dendritic cells targeting peptide) and PorB (the outer membrane pore proteins of N. meningitidis) proteins containing gp67 protein secretion signal peptide were expressed using the baculovirus system for the preparation of subunit vaccines. We used experimental animal rabbits to test immunogenicity to evaluate the effect of the newly constructed PR vaccines., Results: Compared with the PRV-gB subunit vaccine and SD-2017ΔgE/gI inactivated vaccines, rabbits (n = 10) that were intramuscularly vaccinated with SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine showed significantly higher anti-PRV-specific antibodies as well as neutralizing antibodies and IFN-γ levels in serum. In addition, the SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine protected (90-100%) rabbits against homologous infection by the PRV variant strain. No obvious pathological damage was observed in these vaccinated rabbits., Conclusions: The SD-2017ΔgE/gI/TK live attenuated vaccine provided 100% protection against PRV variant challenge. Interestingly, the subunit vaccines with gB protein linked to DCpep and PorB protein as adjuvant may also be a promising and effective PRV variant vaccine candidate., (© 2023. The Author(s).)

Background : A slower progression of AIDS and increased survival in GBV-C positive individuals, compared with GBV-C negative individuals has been demonstrated; while the loss of GBV-C viremia was closely associated with a rise in mortality and increased progression of AIDS. Following on from the previous reported studies that support the thesis that GBV-C E2 interferes with HIV-1 entry, in this work we try to determine the role of the GBV-C E1 protein in HIV-1 inhibition. Methods : The present work involves the construction of several overlapping peptide libraries scanning the GBV-C E1 protein and the evaluation of their anti-HIV activity. Results : Specifically, an 18-mer synthetic peptide from the GBV-C E1 protein, E1(139-156), showed similar antiviral activity against HIVs from viruses from clades A, B, C, D and AE. Competitive ELISA using specific gp41-targeting mAbs, fluorescence resonance energy transfer as well as haemolysis assays demonstrated that this E1 peptide sequence interacts with the highly conserved N-terminal region of the HIV-1 gp41 (the fusion peptide) which is essential for viral entry. Conclusions : We have defined a novel peptide lead compound and described the inhibitory role of a highly conserved fragment of the E1 protein. General Significance : The results together allow us to consider the non-pathogenic E1 GBV-C protein as an attractive source of peptides for the development of novel anti-HIV therapies. [ABSTRACT FROM AUTHOR]

Hepatitis G virus or GB virus C (GBV-C) is a human virus of the Flaviviridae family that is structurally and epidemiologically closest to hepatitis C virus, but replicates primarily in lymphocytes. Co-infection with GBV-C has been reported to confer beneficial outcomes in some HIV-positive patients. Up to now, however, studies on GBV-C infection in the central nervous system (CNS) of HIV-infected patient have rarely been reported. Herein, we report on a 32-year-old HIV-1-infected patient with cerebral toxoplasmosis and fungal encephalitis. GBV-C viral loads were detected in CSF by quantitative real-time reverse transcription polymerase chain reaction (RT–PCR), and the results showed that GBV-C viral load was 6·5 log copies/ml. We amplified and sequenced the E2 and 5′-untranslated regions from the purified viral RNA from CSF by RT–PCR. Both sequences belong to genotype 3 and there were some minor nucleotide divergence among the E2 sequences from the CSF of the patient. These data suggest that GBV-C may be able to penetrate the blood–brain barrier and colonize the CNS of HIV-infected patients. However, the exact mechanisms and potential effect of the infected GBV-C in CNS on HIV-associated neuropathy needs to be further explored. [ABSTRACT FROM PUBLISHER]

The hepatitis G virus (HGV) is a newly discovered RNA virus, which is associated with acute or chronic hepatitis. A survey was conducted in thalassemic patients, intravenous drug users (IVDU) and blood donors aiming to investigate the prevalence of hepatitis G virus (HGV) infection in these groups in Tehran. The presence of HGV RNA in these populations was determined using reverse transcriptase polymerase chain reaction (RT-PCR) of the 5’ non-coding region (NCR) of the virus. One percent of blood donors, 12.9% of thalassemics and 8.8% of the IVDUs, were infected with HGV. Twenty-five percent of HGV positive cases were also positive for HCV and none were positive for HBV-DNA. The greatest proportion of HCV positive cases were seen in IVDU group (67.4%) being the only HIV positive group (8.8%). In conclusion our study showed that HGV infection occurs with relatively intermediate frequency among thalassemics and IVDUs in Iran and a higher rate of HGV-RNA was observed in older IVDUs.

In order to investigate the prevalence of GB virus C (GBV-C)/hepatitis G virus (HGV) infection in dialysis patients and kidney transplant recipients in Central Brazil and also to analyze the virus genotypes distribution, a total of 123 patients including 98 on hemodialysis, 13 on continuous ambulatory peritoneal dialysis treatment, and 12 who received kidney transplantation were interviewed in one unit of dialysis treatment in Goiânia city. Blood samples were collected and serum samples tested for GBV-C/HGV RNA by polymerase chain reaction. Genotypes were determined by restriction fragment length polymorphism (RFLP) analysis. Eighteen samples were GBV-C/HGV RNA-positive, resulting in an overall prevalence of 14.6% (95% CI: 9.2-21.7). A high positivity for GBV-C/HGV RNA was observed in patients who had received kidney transplant (16.7%), followed by those on hemodialysis (15.3%), and peritoneal dialysis (7.7%). RFLP analysis revealed the presence of genotypes 1, 2, and 3 of GBV-C/HGV; more precisely, 9 (50%) samples were found belonging to the 2b subtype, 4 (22%) to the 2a subtype, 3 (17%) to genotype 1, and 2 (11%) to genotype 3. The present data indicate an intermediate prevalence of GBV-C/HGV infection among dialysis patients and kidney transplant recipients in Central Brazil. Genotype 2 (subtype 2b) seems to be the most prevalent GBV-C/HGV genotype in our region.

A survey was conducted in a blood donor population of Central Brazil aiming to investigate the prevalence of GB virus C (GBV-C)/hepatitis G virus (HGV) infection and also to analyze the virus genotypes distribution. A total of 241 voluntary blood donors were interviewed at the State Blood Bank in Goiânia, State of Goiás, Brazil. Blood samples were collected and serum samples tested for GBV-C/HGV RNA by polymerase chain reaction. Genotypes were determined by restriction fragment length polymorphism (RFLP) analysis. Seventeen samples were GBV-C/HGV RNA-positive, resulting in a prevalence of 7.1% (95% CI: 4.2-11.1). A significant trend of GBV-C/HGV RNA positivity in relation to age was observed, with the highest prevalence in donors between 29-39 years old. Ten infected individuals were characterized by reporting parenteral (30%), sexual (18%), both (6%) and intrafamiliar (6%) transmission. However, 7 (40%) GBV-C/HGV RNA-positive donors did not mention any potential transmission route. RFLP analysis revealed the presence of genotypes 1 and 2 of GBV-C/HGV; more precisely, 10 (58.9%) samples were found belonging to the 2b subtype, 4 (23.5%) to the 2a subtype, and 3 (17.6%) to genotype 1. The present data indicate an intermediate endemicity of GBV-C/HGV infection among this blood donor population, and a predominant circulation of genotype 2 (subtype 2b) in Central Brazil.

Introduction: Human pegivirus-1 (HPgV-1) is a so-called commensal virus for which no known associated organ disease has been found to date. Yet, it affects immune-reconstitution as previously studied in the HIV population, in whom active co-infection with HPgV-1 can modulate T and NK cell activation and differentiation leading to a protective effect against the evolution of the disease. Little is known on the effect of HPgV-1 on immune-reconstitution in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients, a patient population in which we and others have previously reported high prevalence of HPgV-1 replication. The aim of this study was to compare the immune reconstitution after allo-HSCT among HPgV-1-viremic and HPgV-1-non-viremic patients., Methods: Within a cohort study of 40 allo-HSCT patients, 20 allo-HSCT recipients positive in plasma sample for HPgV-1 by rRT-PCR during the first year (1, 3, 6, 12 months) after transplantation were matched with 20 allo-HSCT recipients negative for HPgV-1. T and NK cell reconstitution was monitored by flow cytometry in peripheral blood samples from allo-HSCT recipients at the same time points., Results: We observed no significant difference in the absolute number and subsets proportions of CD4 and CD8 T cells between patient groups at any analysed timepoint. We observed a significantly higher absolute number of NK cells at 3 months among HPgV-1-viremic patients. Immunophenotypic analysis showed a significantly higher proportion of CD56 bright NK cells mirrored by a reduced percentage of CD56 dim NK cells in HPgV-1-positive patients during the first 6 months after allo-HSCT. At 6 months post-allo-HSCT, NK cell phenotype significantly differed depending on HPgV-1, HPgV-1-viremic patients displaying NK cells with lower CD16 and CD57 expression compared with HPgV-1-negative patients. In accordance with their less differentiated phenotype, we detected a significantly reduced expression of granzyme B in NK cells in HPgV-1-viremic patients at 6 months., Discussion: Our study shows that HPgV-1-viremic allo-HSCT recipients displayed an impaired NK cell, but not T cell, immune-reconstitution compared with HPgV-1-non-viremic patients, revealing for the first time a potential association between replication of the non-pathogenic HPgV-1 virus and immunomodulation after allo-HSCT., Competing Interests: YC: consulting fees from MSD, Novartis, Incyte, BMS, Pfizer, Abbvie, Roche, Jazz, Gilead, Amgen, Astra-Zeneca, Servier; Travel support from MSD, Roche, Gilead, Amgen, Incyte, Abbvie, Janssen, Astra-Zeneca, Jazz. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pradier, Cordey, Zanella, Melotti, Wang, Mamez, Chalandon, Masouridi-Levrat, Kaiser, Simonetta and Vu.)

Background: GB virus C (GBV-C) or hepatitis G virus (HGV) is a newly discovered and enveloped RNA positive-stranded flavivirus-like particle, which has not yet been proven to have major negative effects on liver. Objectives: Increasing the risk of blood-borne infections in hemodialysis patients is a main health care concern in different countries. Therefore, it is important to estimate the prevalence and risk factors of hepatitis G virus infection in Iranian hemodialysis patients to design standard prevention and treatment plans. Patients and Methods: In this multicenter observational or epidemiologic study, 138 patients who underwent hemodialysis in Iranian Army hospitals in Tehran were included. Serum HIV antibody (Ab), HCV antibody and HBS antigen (Ag) were assessed. Demographic data such as gender, age, blood group, cause of renal failure, dialysis onset and duration were collected from medical files. GBV-C/HGV was evaluated by nested reverse transcription polymerase chain reaction (RT-PCR) method. Then, all data were analyzed by SPSS ver. 13. Results: In total, 81 males and 57 females were included. The mean age of patients was 62.16 ± 14.86 years. Six (4.3%) had positive results for GBV-C/HGV by RT-PCR. Except gender (P = 0.045) and duration of dialysis in a week (P < 0.001), other demographic factors revealed no significant difference (P > 0.05). All patients had negative results for HIV Ab, HCV Ab and HBS Ag. Conclusions: Overall, 4.3% of patients had positive results for GBV-C/HGV and all negative for HIV, HCV and HBV. Further studies are needed to elucidate real prevalence, risk factors and characteristics of HGV infection in Iranian hemodialysis patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effect of GB virus C on laboratory markers and histological parameters among HIV-seropositive patients coinfected with HCV. Lower degrees of hepatic lesions were observed in the triple-infected patients, in comparison with HIV-HCV coinfected patients who were negative for GBV-C RNA.O objetivo do estudo foi avaliar o efeito da infecção pelo vírus GB-C em marcadores laboratoriais e parâmetros histológicos em pacientes HIV soropositivos coinfectados com VHC. Menor grau de lesão hepática foi observado nos pacientes com tripla infecção em comparação aos pacientes coinfectados com VIH-VHC negativos para GBV-C RNA.

The development of peptide fusion inhibitors based on short synthetic peptides represents a promising option in the fight against HIV-1 infection, especially in individuals infected with multiresistant HIV-1 strains. GBV-C has the beneficial effect of retarding the progression of AIDS in people who are co-infected with both the GBV-C and HIV viruses. In previous works, the E1(22–39) GBV-C sequence (E1P8lin) was found to be capable of inhibiting the interaction of HIV-1 FP with bilayers and its cyclic analogue (E1P8cyc) showed a higher anti-HIV-1 activity. In the present work, in an attempt to gain a better understanding of the interaction of E1P8 peptides with HIV-1 FP, we analyzed direct interactions between peptides at the molecular level. Our results support that E1P8cyc might be more potent at blocking HIV-1 entry than E1P8lin as a consequence of the structure induced in the complex formed with HIV-1 FP, which is able to modify the conformation adopted by this functional domain of the HIV-1 gp41 protein in target cell membranes. [ABSTRACT FROM AUTHOR]

North Carolina locates acute HIV cases by pooled nucleic acid testing of HIV-antibody negative serum samples. Here, 224 pools of 80 HIV-negative samples (N = 17,920) were screened for viral RNA from HCV, GBV-C, and influenza A. No evidence of influenza A was found, but HCV and GBV-C were common (1.2% and 1.7% prevalence, respectively), demonstrating the utility of pooled testing in locating individuals that may remain undiagnosed otherwise. By sequencing positive pools, potential transmission clusters may be located as well. J. Med. Virol. 86:473-477, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Introduction: GB virus C (GBV-C) or hepatitis G virus (HGV) is an enveloped, RNA positive-stranded flavivirus-like particle. E2 envelope protein of GBV-C plays an important role in virus entry into the cytosol, genotyping and as a marker for diagnosing GBV-C infections. Also, there is discussion on relations between E2 protein and gp41 protein of HIV. The purposes of our study are to multi aspect molecular evaluation of GB virus C E2 protein from its characteristics, mutations, structures and antigenicity which would help to new directions for future researches. Evidence Acquisition: Briefly, steps followed here were; retrieving reference sequences of E2 protein, entropy plot evaluation for finding the mutational /conservative regions, analyzing potential Glycosylation, Phosphorylation and Palmitoylation sites, prediction of primary, secondary and tertiary structures, then amino acid distributions and transmembrane topology, prediction of T and B cell epitopes, and finally visualization of epitopes and variations regions in 3D structure. Results: Based on the entropy plot, 3 hypervariable regions (HVR) observed along E2 protein located in residues 133-135, 256-260 and 279 -281. Analyzing primary structure of protein sequence revealed basic nature, instability, and low hydrophilicity of this protein. Transmembrane topology prediction showed that residues 257-270 presented outside, while residues 234- 256 and 271-293 were transmembrane regions. Just one N-glycosylation site, 5 potential phosphorylated peptides and two palmitoylation were found. Secondary structure revealed that this protein has 6 α-helix, 12 β-strand 17 Coil structures. Prediction of T-cell epitopes based on HLA-A*02:01 showed that epitope NH3- LLLDFVFVL-COOH is the best antigen icepitope. Comparative analysis for consensus B-cell epitopes regarding transmembrane topolo gy, based on physico-chemical and machine learning approaches revealed that residue 231- 296 (NH2- EARLVPLILLLLWWWVNQLAVLGLPAVEAA VAGEVFAGPALSWCLGLPVVSMILGLANLVLYFRWL-COOH) is most effective and probable B cell epitope for E2 protein. Conclusions: The comprehensive analysis of a protein with important roles has never been easy, and in case of E2 envelope glycoprotein of HGV, there is no much data on its molecular and immunological features, clinical significance and its pathogenic potential in hepatitis or any other GBV-C related diseases. So, results of the present study may explain some structural, physiological and immunological functions of this protein in GBV-C, as well as designing new diagnostic kits and besides, help to better understandingE2 protein characteristic and other members of Flavivirus family, especially HCV. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Viruses are candidate causative agents in the pathogenesis of autoimmune (type 1) diabetes. We hypothesised that children with a rapid onset of type 1 diabetes may have been exposed to such agents shortly before the initiation of islet autoimmunity, possibly at high dose, and thus study of these children could help identify viruses involved in the development of autoimmune diabetes. Methods: We used next-generation sequencing to search for viruses in plasma samples and examined the history of infection and fever in children enrolled in The Environmental Determinants of Diabetes in the Young (TEDDY) study who progressed to type 1 diabetes within 6 months from the appearance of islet autoimmunity, and in matched islet-autoantibody-negative controls. Results: Viruses were not detected more frequently in plasma from rapid-onset patients than in controls during the period surrounding seroconversion. In addition, infection histories were found to be similar between children with rapid-onset diabetes and control children, although episodes of fever were reported less frequently in children with rapid-onset diabetes. Conclusions/interpretation: These findings do not support the presence of viraemia around the time of seroconversion in young children with rapid-onset type 1 diabetes. [ABSTRACT FROM AUTHOR]

GB virus C (GBV-C), a human virus of the Flaviviridae family that is structurally and epidemiologically closest to hepatitis C virus (HCV), has been reported to confer beneficial outcomes in HIV-positive patients. However, the prevalence of GBV-C in HIV-positive individuals in Indonesia is unknown. Since GBV-C is more prevalent in anti-HCV positive patients than in anti-HCV negative subjects, transmission of GBV-C and HCV could be by the same method. This study examined the prevalence and molecular characteristics of GBV-C infection in HIV patients in Yogyakarta, Indonesia. The prevalence of GBV-C among HIV patients ( n = 125, median age 31 years) based on the 5′UTR region was 111/125 (88.8%), including 39/48 (81.3%) and 72/77 (93.5%) HIV-infected patients with and without HCV infection, respectively. GBV-C isolates were of genotype 2a, 3 and 6 in 58.3%, 12.6% and 28.4% of patients, respectively. Patients with genotype 3 were significantly younger than those with genotypes 2a or 6 ( P = 0.001 and P = 0.012, respectively). Genotypes 3 and 6 were significantly associated with injection drug use ( P = 0.004 and P = 0.002, respectively) and HCV co-infection ( P < 0.001 for both genotypes), indicating a shared transmission route with HCV. In conclusion, the prevalence of GBV-C among HIV-positive patients in Indonesia is high, and three genotypes were detected, namely genotype 2a, 3 and 6. [ABSTRACT FROM AUTHOR]

GB virus C (GBV-C) is frequently identified in patients co-infected with human immunodeficiency virus type 1 (HIV-1) due to the similar transmission routes. However, it remains unclear how these two viruses interact with each other and how one virus affects the replication of the other in the human body. In this study, we performed a case-control study to determine whether GBV-C viraemia could prevent the acquisition of HIV-1 infection, and a cohort study to determine the prevalence, genotypic characteristics and incidence of GBV-C infection in men who have sex with men (MSM) populations in Beijing, China. The prevalence of GBV-C infection in HIV-1-negative subjects was similar to that in HIV-1-positive subjects. Before HIV-1 acquisition, the prevalence of GBV-C was 17·7%, which increased to 27·2% at the acute stage and to 34% at the chronic stage. Genotype 3 was the major genotype of GBV-C in both groups. A significantly positive correlation was observed between the CD4+ T-cell counts and GBV-C viral loads at the acute stage of HIV infection. At the chronic stage (12 months later), this correlation was no longer significant, although it was still positive. Overall, this study demonstrated that pre-existing GBV-C viraemia could not prevent the acquisition of HIV-1 infection and transmission of HIV-1 significantly increased the prevalence of GBV-C viraemia. [ABSTRACT FROM AUTHOR]

GB Virus C (GBV-C) has been associated with a better prognosis of HIV-1 disease in adults. Little is known about prevalence and interaction between GBV-C, HIV-1, and/or hepatitis C virus (HCV) in hemophiliac children and adolescents.A well-characterized cohort of HIV-1-infected and HIV-1-uninfected hemophiliac children and adolescents followed in the Hemophilia Growth and Development Study (HGDS) were evaluated using quantitative reverse transcription polymerase chain reaction to detect GBV-C RNA in samples from baseline and last follow-up visit.HIV-1-infected (n = 202) and HIV-1-uninfected (n = 119) patients had a low prevalence of GBV-C infection at baseline (0.9 and 0%), which increased at time of last follow-up visit to 25.2% and 26.3%, respectively. In addition, at the time of the follow-up GBV-C measurement, those GBV-C infected had been followed longer and had higher CD4+ cell counts and lower HIV-1 viral loads than those GBV-C uninfected. These beneficial effects of GBV-C were no longer significant after controlling for CD4+ cell count and HIV-1 RNA at baseline. HCV RNA clearance was more common amongst those who were not GBV-C infected than those who became GBV-C viremic.This study confirms a positive association of GBV-C with milder course of HIV-1 infection. GBV-C infection was associated with a higher likelihood of persistent HCV infection. [ABSTRACT FROM AUTHOR]

Synthetic peptides derived from GB virus C (GBV-C) have previously been studied in our group for the development of new systems capable of diagnosing diseases caused by this humanotropic virus. We also recently described specific peptide domains of the E2 envelop protein of GBV-C that have the capacity to interfere with the HIV-1 fusion peptide, produce a notable decrease in cellular membrane fusion, and perturb HIV-1 infectivity in a dose-dependent manner. The present work discloses the design and synthesis of both linear and cyclic branched peptides based on a previously reported N-terminal sequence of the GBV-C E2 protein. Immunoassays and cell-cell fusion assays were performed to evaluate their diagnostic value to detect anti-GBV-C antibodies in HIV-1 patients, as well as their putative anti-HIV-1 activity as entry inhibitors. Our results showed that chemical modifications of the selected E2(7-26) linear peptide to afford cyclic architecture do not result in an enhanced inhibition of gp41 HIV-1-mediated cell-cell fusion nor improved sensitivity in the detection of GBV-C antibodies in HIV-1 co-infected patients. Thus, the ELISA data reinforce the potential utility of linear versions of the E2(7-26) region for the development of new peptide-based immunosensor devices for the detection of anti-GBV-C antibodies in HIV-1 co-infected patients. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: The picture that has emerged from studies investigating HIV infected people with GBV-C viremia is that they have lower plasma HIV viral loads in comparison with HIV-positive people who did not have the GBV-C viremia. Objectives: Since GBV-C HIV coinfection has not been studied in Iran, we have designed a survey to study the outcomes of GBV-C infection on HIV infected individuals. Patients and Methods: We analyzed 78 serum samples from HIV-positive patients in Tehran. The HIV positive statue was confirmed by Western blot in our laboratory. Next we detected GBV-C RNA by RT nested-PCR and divided our patient into GBV-C positive and GBV-C negative groups. The final step was measuring the CD4 count and HIV viral load and comparing the means of the CD4 count and HIV viral load in HIV-infected individuals in the GBV-C positive and GBV-C negative groups. Results: We detected GBV-C RNA in 15 patients out of 78. The mean CD4 count was 607.13 compared to 415.87 in the GBV-C negative group and the difference was significant (P = 0.005). In contrast to the CD4 count there was no significant difference in HIV viral loads between HIV infected individuals in the GBV-C positive and GBV-C negative groups. Conclusion: Although there was no significant difference in the mean of the HIV viral load between the GBV-C positive and GBV-C negative groups, the significantly higher CD4 mean in the GBV-C positive group compared with the GBV-C negative group suggests a beneficial effect of this coinfection. [ABSTRACT FROM AUTHOR]

The beneficial effect of co-infection by GB virus C (GBV-C) in the course of the disease in human immunodeficiency virus (HIV)-infected patients has been described, although its mechanism of action is yet to be determined. The role of anti-GBV-C antibodies in HIV-infected patients also remains unknown. At present, there are no commercial systems to detect specific markers of GBV-C infection. The research presented follows our previous work from which we obtained chimeric molecules formed by two domains of different GBV-C proteins with good sensitivity ⁄ specificity balances in the detection of anti-GBV C antibodies in hemodialyzed and chronic hepatitis patient samples. It has been investigated the ability of the synthetic peptides to recognize specific anti-GBVC antibodies in HIV and HCV⁄ HIV co-infected patients by a peptide-based ELISA immunoassay. The results showed that human immunodeficiency virus-infected patients have a significantly higher frequency of anti-GBV-C antibodies than healthy controls. A comparison between HCV+ ⁄ HIV+ and HCV) ⁄ HIV+ was analyzed. Although a higher percentage of HCV⁄ HIV-positive sera were positive for antibodies against GBV-C peptides, the difference was not significant. The presence of anti- GBV-C antibodies could represent a good marker of exposure to GBV-C in HIV infected patients to facilitate a further analysis of the effect of this exposure in the progression of illness caused by HIV infection. [ABSTRACT FROM AUTHOR]

This study was undertaken to evaluate the prevalence of GB virus C (GBV-C) viraemia and anti-E2 antibody, and to assess the effect of co-infection with GBV-C and HIV during a 10-year follow-up of a cohort of 248 HIV-infected women. Laboratory variables (mean and median CD4 counts, and HIV and GBV-C viral loads) and clinical parameters were investigated. At baseline, 115 women had past exposure to GBV-C: 57 (23%) were GBV-C RNA positive and 58 (23%) were anti-E2 positive. There was no statistical difference between the groups (GBV-C RNA þ /anti-E2 2 , GBV-C RNA 2 /anti-E2 þ and GBV-C RNA 2 /anti-E2 2 ) regarding baseline CD4 counts or HIV viral loads (P ¼ 0.360 and 0.713, respectively). Relative risk of death for the GBV-C RNA þ /anti-E2 2 group was 63% lower than that for the GBV-C RNA 2 /anti-E2 2 group. Multivariate analysis demonstrated that only HIV loads ≥100,000 copies/mL and AIDS-defining illness during follow-up were associated with shorter survival after AIDS development. It is likely that antiretroviral therapy (ART) use in our cohort blurred a putative protective effect related to the presence of GBV-C RNA. [ABSTRACT FROM AUTHOR]

Abstract: The use of synthetic peptides of both structural and nonstructural proteins of GB virus C (GBV-C) has been studied for the development of new systems to diagnose infection caused by this virus. In an attempt to increase the antigenicity of linear peptide sequences, chimeric multiple antigenic peptides (MAPs) containing epitopes from E2, NS4, and NS5 GBV-C proteins have been synthesized. The synthetic constructs were evaluated by ELISA to establish whether the epitopes in chimeric branched peptides are more efficiently recognized by the specific antibodies compared to the monomeric linear sequences. Moreover, we have investigated the application of a commercial biosensor instrument for the detection of antibodies against the GBV-C in human serum samples. The results of the immunoassays reported in this work highlight the usefulness of synthetic tetrameric branched peptides containing sequences from envelope and nonstructural GBV-C proteins for the diagnosis of GBV-C infection. The potential clinical value of the MAP4(E2-NS5a) for the serodiagnosis of GBV-C infection was demonstrated, thus providing the basis for performing prevalence studies of the infection among the hemodialyzed and hepatitis C virus (HCV)-infected population. [Copyright &y& Elsevier]

Abstract: Studies of GB virus type C (GBV-C) replication in vitro have been limited because of poor growth of GBV-C in cell culture. In order to address the infection of GBV-C, two GBV-C subgenomic replicons (GBCrepEGFP and GBCrepTNF) were developed from a GBV-C full-length genomic cDNA. The viral replication, protein expression and the production of virus-like particles were evaluated in human hepatoma cell line Huh7. The results showed that the established GBCrepEGFP and GBCrepTNF replicons could be replicated autonomously and expressed in cell culture for at least 2 months and 1 month respectively. The replicon RNA could assemble RNA-containing structures in the HuhEH cells expressing GBV-C structural proteins. It suggests that a cell line supporting the replication of GBV-C was established. This replicon system might be used to understand better the biology of GBV-C. [Copyright &y& Elsevier]

To determine the prevalence and incidence of hepatitis C virus (HCV) infections among haemodialysis patients, a large prospective multicentre trial was conducted in the German Federal State of North Rhine-Westphalia. Sera obtained from the recruited patients in two separate sampling rounds run 1 year apart were analysed for both anti-HCV antibodies and HCV RNA. HCV RNA positive samples were also genotyped by direct sequencing of an HCV core fragment. In the first and second rounds, 150 (5.2%) of 2909 and 114 (5.4%) of 2100 patients were anti-HCV positive, respectively, and 4% of individuals were viraemic. Evaluation of potential risk factors in a case–control study indicated that the factors ‘foreign country of birth’, ‘blood transfusions given before 1991’ and ‘duration of treatment on haemodialysis’ were associated with the risk of HCV infection. Among the 2100 patients of whom ‘paired’ serum samples from both rounds were available for testing, not a single ‘ de novo’ HCV infection could be recorded. The fact that in a subset of about 20% of these patients no nosocomial GB virus C (GBV-C) transmission occurred during the observational period suggests that the lack of HCV seroconversions was not only attributable to the isolation of HCV-infected patients but also to the strict adherence to so-called universal hygienic precautions for infection control maintained in the participating dialysis centres. [ABSTRACT FROM AUTHOR]