GB Virus C RNA Research Articles

The APOBEC3B deletion polymorphism is associated with prevalence of hepatitis B virus, hepatitis C virus, Torque Teno virus, and Toxoplasma gondii co-infection among HIV-infected individuals

BackgroundData regarding the influence of the APOBEC3B deletion on infectious diseases remain limited and shown discrepancies. ObjectivesTo characterize the APOBEC3B deletion polymorphism status and its association with prevalence of co-infection with blood-borne pathogens in Indonesian HIV-infected individuals. Materials and methodsA total of 597 HIV-positive blood samples were tested for the hepatitis B virus (HBV), hepatitis C virus (HCV), Torque Teno virus (TTV), GB virus-C (GBV-C), and Toxoplasma gondii. Nucleic acid was extracted from plasma samples and used for the molecular detection of HIV RNA, HBV DNA, HCV RNA, TTV DNA, and GBV-C RNA, whereas HBsAg, anti-HCV, IgM and IgG anti-T. gondii were detected through serological testing. The APOBEC3B deletion polymorphism was genotyped by polymerase chain reaction (PCR). ResultsThe deletion genotype was associated with HCV viremia (p<0.001) as well as elevated IgG anti-T. gondii (adjusted OR [aOR]=3.4). The deletion genotype was also associated with decreased levels of HBsAg (aOR=0.03), and anti-HCV (aOR=0.1). D/D was frequently found in HIV-infected individuals with CD4+T cells<14% (aOR=5.8). The intact genotype was associated with a reduced likelihood of a CD4+T cell count<200 cells/μL (aOR=0.2) but a higher prevalence of TTV co-infection (aOR=8.6). ConclusionsThe APOBEC3B deletion polymorphism was found to be associated with HBV, HCV, TTV, and T. gondii co-infection in Indonesian HIV-infected individuals.

GBV-C infection and risk of NHL among U.S. adults.

Some retrospective studies suggest an association between infection with GB virus-C (GBV-C) and non-Hodgkin lymphoma (NHL). We evaluated this association prospectively in a nested case-control study within the U.S. Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Cases (N = 658) and controls (N = 1,316) were individually matched by age, sex, race/ethnicity, timing of study entry, and sample selection. Prediagnostic PLCO serum samples were tested for GBV-C RNA (as a measure of active infection) and E2 antibody (active or resolved infection). Logistic regression was used to estimate odds ratios (OR) for the association between GBV-C and NHL overall and NHL subtypes. Twelve cases (1.8%) and seven controls (0.5%) were GBV-C RNA-positive. GBV-C RNA positivity was associated with NHL overall [OR, 3.43; 95% confidence interval (CI), 1.35-8.71] and, based on small numbers, diffuse large B-cell lymphoma (OR, 5.31; 95% CI, 1.54-18.36). The association with NHL persisted when the interval between testing and selection was greater than 4 years (OR, 6.00; 95% CI, 1.21-29.73). In contrast, E2 antibody positivity was not associated with NHL risk (OR, 1.08; 95% CI, 0.74-1.58). Our study demonstrates that GBV-C infection precedes development of NHL. GBV-C infection may play an etiologic role in a small proportion of NHL cases, perhaps by causing chronic immune stimulation or impaired immunosurveillance.

HIV-1 and GBV-C co-infection in Venezuela.

Co-infection with GB virus C (GBV-C) in patients infected with human immunodeficiency virus 1 (HIV-1) has been associated with prolonged survival. The aim of this study was to evaluate the prevalence of GBV-C infection among HIV-1-infected patients in Venezuela, and to determine the effects of the co-infection on the levels of relevant cytokines. Plasma samples were collected from 270 HIV-1-seronegative and 255 HIV-1-seropositive individuals. GBV-C infection was determined by RT-PCR of the NS5 region and genotyped by sequence analysis of the 5´UTR region. HIV-1 strains were characterized by sequence analysis of pol, vif, env, and nef genes. Selected cytokines were evaluated by ELISA. Ninety-seven of 525 (18.5%) plasma samples tested positive for GBV-C RNA. A significantly higher prevalence of GBV-C was found among HIV-1 patients compared to HIV-1-seronegative individuals (67/255, 26% versus 30/270, 11%; p < 0.001). Statistical difference was observed in the viral load between HIV-1+GBV-C+ and HIV-1+GBV-C- (p = 0.014), although no differences in CD4+ cell counts were found between both groups. TNFα concentration was higher in HIV-1+GBV-C- than in HIV-1+GBV-C+ patients (25.9 pg/mL versus 17.3 pg/mL; p = 0.02); RANTES expression levels were more variable in GBV-C co-infected patients and more frequently elevated in HIV-1 mono-infected patients compared to patients co-infected with GBV-C. The previously observed beneficial effect of co-infection with HIV-1 and GBV-C on disease progression is complex and might be due in part to a change in the cytokine environment. More studies are required to understand the interaction between both viruses.

Impact of GB virus C viraemia on clinical outcome in HIV‐1‐infected patients: a 20‐year follow‐up study

The impact of coexisting GB virus C (GBV-C) infection on the clinical course of HIV infection remains controversial. Early data from HIV-1 infected patients attending the Hannover Medical School in 2001 suggested prognostic benefit in GBV-C viraemic patients. The aim of this study was to evaluate patterns in long-term mortality and morbidity outcomes in this cohort. The impact of the introduction of antiretroviral therapy (ART) on the perceived benefits of GBV-C viraemia was subsequently investigated. A retrospective follow-up analysis of data in this cohort was performed. GBV-C status (GBV-C RNA positive, antibodies against GBV-C envelope protein E2 or no evidence of GBV-C exposure) had been determined at enrolment, with several markers of HIV disease progression (such as viral load and CD4 cell count) being collated from 1993/1994, 2000 and 2012. These eras were chosen to reflect variations in treatment strategies within the cohort. In addition, mortality and HIV-related morbidity data were collated for all patients. Complete data were available for 156 of 197 patients (79%). In highly active antiretroviral therapy (HAART)-naïve patients, GBV-C RNA positivity conferred significant improvements in the course of HIV infection and mortality as well as lower rates of HIV-related diseases. E2 positivity alone conferred no significant advantage. With the advent of HAART, however, the benefits GBV-C RNA positivity disappeared. Although GBV-C coinfection appears to inherently improve morbidity and mortality in HIV-infected patients, modern HAART has eradicated these advantages. Evidence of synergy between GBV-C status and HAART response exists, with further studies examining the role of GBV-C in existing treatment de-escalation strategies being required.

Abstract 2538: GB virus C viremia and subsequent risk of non-Hodgkin lymphoma in the PLCO screening trial.

Abstract Background: Immune disturbance and chronic infections contribute to the development of non-Hodgkin lymphoma (NHL). GB virus C (GBV-C), a flavivirus, causes chronic asymptomatic infection in 1-2% of blood donors. Retrospective case-control studies have demonstrated associations between GBV-C viremia and NHL, but the prevalence of GBV-C could be artifactually high in NHL cases due to prior blood transfusions or disease-related immunosuppression and viral reactivation. Methods: We conducted a case-control study nested in the U.S. Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial. Using incidence density sampling, NHL cases were each matched to 2 controls on sex, race, and age and calendar year at cohort entry. Pre-diagnostic sera were assessed for GBV-C RNA in matched sets, with the laboratory blinded to case-control status. GBV RNA positivity was determined by a consensus algorithm incorporating results of 5 reverse transcriptase PCR assays. Odds ratios (ORs) for NHL overall and NHL subtypes were calculated using conditional and unconditional logistic regression, respectively. Results: 658 NHL cases and 1316 controls were included. GBV-C RNA was detected in 37 subjects (1.9%). Notably, in contrast to the low prevalence in study subjects, blinded testing concurrently found GBV-C RNA in 24 of 25 (96%) positive quality control (QC) samples but also 14 of 25 (56%) of negative QC samples, likely reflecting contamination when the QC samples had been prepared. Nonetheless, among subjects GBV-C RNA tended to be more commonly detected in cases than controls (2.6% vs. 1.5%, OR 1.73, 95%CI 0.90-3.34, p=0.10). The association with NHL was strongest over longer latency intervals, with ORs (95%CI) of 1.56 (0.58-4.18), 0.88 (0.26-2.99), and 6.00 (1.21-29.7) for GBV-C RNA detected 0-1.0, 1.1-4.0, and 4.1+ years, respectively, before diagnosis/selection. Among NHL subtypes, we observed non-significant associations with GBV-C RNA for diffuse large B-cell lymphoma (OR 1.84, 95%CI 0.62-5.45), follicular lymphoma (2.29, 0.67-7.85), and chronic lymphocytic leukemia (2.15, 0.94-4.94). Conclusions: GBV-C viremia was associated with a non-significant increased risk of NHL in a U.S. general population cohort. The presence of an association more than 4 years after detection of GBV-C RNA argues against bias related to NHL treatment or immunosuppression in cases, and lends support to a possible etiologic relationship. Detection of low-level GBV-C viremia was challenging, and contamination during sample preparation likely led to a high prevalence of RNA positivity in negative QC samples. Contamination should not have led to preferentially higher positivity in cases vs. controls, but we are undertaking additional confirmatory testing. Samples will also be assayed for infection with HIV and hepatitis C virus, which are proven viral causes of NHL and are more common in GBV-C infected individuals. Citation Format: Cindy Chang, Jack Stapleton, Donna Klinzman, Lars Larson, Hormuzd Katki, Mark Purdue, Eric A. Engels. GB virus C viremia and subsequent risk of non-Hodgkin lymphoma in the PLCO screening trial. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2538. doi:10.1158/1538-7445.AM2013-2538

GB Virus C Infection among Lithuanian Population with Hepatitis C (HCV) Virus Infection

Background: GB virus C (GBV-C), also known as hepatitis G virus (HGV), is an enveloped virus with about 9,4Kb genome-length single-strand RNA. Based on similarity in genome structure with HCV, the GBV-C virus is classified as the Flaviviridae family virus. The GBV-C virus has a worldwide distribution and virus infections are common among healthy blood donors as well as among immunocompromised individuals. Previous studies showed the high GBV-C co-infection rate in hepatitis C virus (HCV) and Human immunodeficiency virus (HIV) positive individuals. Based on genetic differences between the 5′ untranslated region (5′UTR) sequences of GBV-C isolates, virus is classified into seven major genotypes and in several subtypes. The distribution of GBV-C genotypes varies geographically and information is still incomplete. The aim of this study was to determine the frequency the frequency of GBV-C and the GBV-C genotypes among the HCV positive individuals in Lithuania. Methods: In this study, GBV-C RNA was isolated from serum samples of 170 patients with known HCV infection. The nested reverse transcriptase reaction was used to synthesize the complementary DNA (cDNA) and the fragment of 210 bp from 5′UTR region was amplified by nested RT PCR. The PCR products were sequenced and subjected to phylogenetic analysis by using reference sequences from each genotype obtained from GenBank (n=46). The analysis was computed using CLC bio version 6.6.5 and MEGA 5.2. Results: Among 170 HCV positive patients, 36 (21.17%) were positive for GBV-C. Based on phylogenetic analysis of a short region (210 bp) in 5′UTR region two genotypes, 2a and 3 were classified. Conclusions: In this study it was found a high frequency of the GBV-C genotype 2a in Lithuanian HCV positive patients. The presence of the genotype 3 may be correlated to the geographical location and history of Lithuania.

Role of GB Virus C in HIV-1–Infected and Hepatitis C Virus–Infected Hemophiliac Children and Adolescents

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.

Role of GB Virus C in Human Immunodeficiency Virus Type-1- and Hepatitis C Virus-infected Hemophiliac Children and Adolescents

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.

Transmission of GB Virus Type C via Transfusion in a Cohort of HIV-Infected Patients

GB virus C (GBV-C) infection is transmitted by blood exposure and associated with lower human immunodeficiency virus (HIV) load and slower HIV disease progression. Few studies describe predictors of acute GBV-C infection following transfusion in HIV-infected patients. We used a limited-access database from the National Heart Lung and Blood Institute's Viral Activation Transfusion Study, a randomized controlled trial of leukoreduced versus nonleukoreduced transfusions received by HIV-infected, transfusion-naive patients. Blood samples from 489 subjects were tested for GBV-C markers in pretransfusion and posttransfusion samples. We estimated the risk of acquiring GBV-C RNA and predictors of GBV-C acquisition, using pooled logistic regression. GBV-C RNA was detected ≤120 days following the first transfusion in 22 (7.5%) of 294 subjects who were GBV-C negative before transfusion. The risk of GBV-C RNA acquisition increased with each unit transfused (odds ratio, 1.09; 95% confidence interval, 1.06-1.11). Lower baseline HIV load and use of antiretroviral therapy were associated with subsequent GBV-C RNA acquisition, after control for units of blood transfused. Leukoreduced status of transfused units was not associated with GBV-C transmission. Blood transfusion is associated with a significant risk of GBV-C acquisition among HIV-infected patients. Transmission of GBV-C by blood transfusion was inversely related to HIV load.

A Novel Genotype of GB Virus C: Its Identification and Predominance among Injecting Drug Users in Yunnan, China

GB virus C (GBV-C) is prevalent globally and particularly among individuals at risk of parental exposures. Based on genetic diversity, this virus is now classified into six genotypes and many subtypes with distinct geographical distribution. In this study, 120 Injecting Drug Users (IDUs) were recruited from Yunnan province, China. Among them, 43 (35.8%) were positive for GBV-C RNA, 70 (58.3%) and 103 (85.8%) sero-positive for HIV-1 and HCV respectively. This revealed 18.3% of IDUs having GBV-C/HIV/HCV triple infection, which is significantly higher than 7.5% of GBV-C/HIV-1 and 10% of GBV-C/HCV dual infection rates (P<0.05). Based on 5′UTR sequences, the identified 43 viral isolates can be classified into three phylogenetic groups: one (2.3%) and two (4.7%) belonged to genotype 3 and 4, respectively, and the remaining 40 (93%) formed a new group with 97% of bootstrap support. This new GBV-C group was further confirmed by characterizing the E2 region and full-length genome sequences. Analysis of 187 nt 5′UTR sequence showed three previous reported isolates from Southeast Asia were re-classified into this new group. It implies they have the same origin with strains from Yunnan. Although we provisionally assigned this new group as GBV-C genotype 7, a simpler five groups of GBV-C nomenclature is recommended. Genotype 4, 6 and the newly designated genotype 7 could be reclassified as one group, which may represent a single GBV-C genotype. The classification of the other four groups was corresponding to that of previous reported genotype 1, 2, 3 and 5. Furthermore, the diversity of amino acid sequence in the E2 region was analyzed. The inhibitory effect of GBV-C genotype 7 on HIV-1 cell entry could be deduced. Since GBV-C may have a beneficial effect on AIDS disease progression and interact with HCV during co-infection, this finding may raise interests in future studies on this virus that was previously thought to be a “non-pathogenic virus”.

Prevalence, incidence density, and genotype distribution of GB virus C infection in a cohort of recently HIV-1-infected subjects in Sao Paulo, Brazil.

BackgroundThe results of previous studies elsewhere have indicated that GB virus C (GBV-C) infection is frequent in patients infected with the human immunodeficiency virus type 1 (HIV-1) due to similar transmission routes of both viruses. The aim of this study was to determine the prevalence, incidence density and genotypic characteristics of GBV-C in this population.Methodology/Principal FindingsThe study population included 233 patients from a cohort primarily comprised of homosexual men recently infected with HIV-1 in São Paulo, Brazil. The presence of GBV-C RNA was determined in plasma samples by reverse transcriptase-nested polymerase chain reaction and quantified by real-time PCR. GBV-C genotypes were determined by direct sequencing. HIV viral load, CD4+ T lymphocyte and CD8+ T lymphocyte count were also tested in all patients. The overall prevalence of GBV-C infection was 0.23 (95% CI: 0.18 to 0.29) in the study group. There was no significant difference between patients with and without GBV-C infection and Glycoprotein E2 antibody presence regarding age, sex, HIV-1 viral load, CD4+ and CD8+T cell counts and treatment with antiretroviral drugs. An inverse correlation was observed between GBV-C and HIV-1 loads at enrollment and after one year. Also, a positive but not significant correlation was observed between GBV-C load and CD4+ T lymphocyte. Phylogenetic analysis of the GBV-C isolates revealed the presence of genotype 1 and genotype 2, these sub classified into subtype 2a and 2b.Conclusion/SignificanceGBV-C infection is common in recently HIV -1 infected patients in Sao Paulo, Brazil and the predominant genotype is 2b. This study provides the first report of the GBV-C prevalence at the time of diagnosis of HIV-1 and the incidence density of GBV-C infection in one year.

Influence of hepatitis G virus (GB virus C) on the prognosis of HIV-infected women

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 + /anti-E2 - , GBV-C RNA - /anti-E2 + and GBV-C RNA - /anti-E2 - ) regarding baseline CD4 counts or HIV viral loads (P = 0.360 and 0.713, respectively). Relative risk of death for the GBV-C RNA + /anti-E2 - group was 63% lower than that for the GBV-C RNA - /anti-E2 - 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.

Evidence for extensive genotypic diversity and recombination of GB virus C (GBV-C) in Germany

Multiple genotypes of GB virus C (GBV-C)-a non-pathogenic flavivirus-have been identified to date, although they are not uniformly distributed worldwide. It has also been suggested that GBV-C genotype may play a role in modulating HIV disease; however, the prevalence and genotype distribution of GBV-C has not been adequately studied in most countries. Among 408 HIV positive subjects in Germany, 97 (23.8%) had detectable GBV-C RNA. Based on sequencing of the 5' untranslated region (5'-UTR), the GBV-C genotypes were 1 (n=8; 8.2%), 2 (n=81; 83.5%), and 3 (n=2; 2.1%), as well as a unique genotype not previously reported (n=6; 6.2%). Among 17 samples also sequenced in the envelope 2 (E2) region, 14 had concordant genotype results when comparing the 5'-UTR and E2, while evidence of intergenotypic recombination was observed among E2 sequences from 3 individuals. These results suggest that genotypic diversity and viral recombination contribute to the overall genetic variability of GBV-C.

Down-regulation of intra-hepatic T-cell signaling associated with GB virus C in a HCV/HIV co-infected group with reduced liver disease

Studies have shown that GB virus C (GBV-C) infection leads to reduced liver disease in hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection. Considering that the underlying mechanism(s) are unknown, we aim to identify differential gene and protein expression associated with GBV-C in HCV/HIV co-infection that may be responsible for reduced liver disease. Liver, peripheral blood mononuclear cells (PBMCs), and plasma samples were collected from 43 HCV/HIV patients. Plasma was tested for GBV-C RNA by RT-PCR with NS5B gene primers. A microarray was performed on the liver and RT-qPCRs on the liver/PBMC samples. Hepatic protein expression was measured by immunohistochemistry. Sixteen out of 43 patients had GBV-C RNA. GBV-C was associated with reduced hepatic fibrosis (p=0.005) and inflammation (p=0.007). The microarray analysis of the liver samples (n=10) showed down-regulation of genes critical to intra-hepatic T-cell signaling associated with GBV-C. Quantitative RT-PCR of the liver samples (n=13) confirmed the down-regulation of lymphocyte-specific protein tyrosine kinase (LCK) (p=0.02) and docking protein 2 (DOK2) (p=0.04). No differences in the expression levels of these genes were observed in PBMCs (n=22) according to the GBV-C status. The hepatic expression of the LCK protein, measured by immunohistochemistry (n=36), was decreased in CD3-positive T-cells within portal tracts associated with GBV-C (p=0.003). This remained significant in multivariate analysis controlling for hepatic fibrosis and inflammation (p=0.027). No differences were observed in plasma cytokine concentrations (n=25) or ex-vivo peripheral T-cell responses (n=13) versus GBV-C status. GBV-C infection is associated with down-regulation of critical genes involved in intra-hepatic T-cell signaling in HCV/HIV co-infection. This may be relevant to the pathogenesis of reduced HCV-related liver disease in HIV co-infection.

Prevalence and correlates of GB virus C infection in HIV‐infected and HIV‐uninfected pregnant women in Bangkok, Thailand

GB virus C (GBV-C) is an apathogenic virus that has been shown to inhibit HIV replication. This study examined the prevalence and correlates of GBV-C infection and clearance in three cohorts of pregnant women in Thailand. The study population consisted of 1,719 (1,387 HIV-infected and 332 HIV-uninfected) women from three Bangkok perinatal HIV transmission studies. Stored blood was tested for GBV-C RNA, GBV-C antibody, and if RNA-positive, genotype. Risk factors associated with the prevalence of GBV-C infection (defined as presence of GBV-C RNA and/or antibody) and viral clearance (defined as presence of GBV-C antibody in the absence of RNA) among women with GBV-C infection were examined using multiple logistic regression. The prevalence of GBV-C infection was 33% among HIV-infected women and 15% among HIV-uninfected women. GBV-C infection was independently associated (AOR, 95% CI) with an increasing number of lifetime sexual partners (referent-1 partner, 2 partners [1.60, 1.22-2.08], 3-10 partners [1.92, 1.39-2.67], >10 partners [2.19, 1.33-3.62]); injection drug use (5.50, 2.12-14.2); and HIV infection (3.79, 2.58-5.59). Clearance of GBV-C RNA among women with evidence of GBV-C infection was independently associated with increasing age in years (referent <20, 20-29 [2.01, 1.06-3.79] and ≥30 [3.18, 1.53-6.60]), more than 10 lifetime sexual partners (3.05, 1.38-6.75), and HIV infection (0.29, 0.14-0.59). This study found that GBV-C infection is a common infection among Thai women and is associated with HIV infection and both sexual and parenteral risk behaviors.

No increased incidence for GB‐virus C infection in a cohort of HIV‐positive lymphoma patients

Dear Sir, Until recently no pathogenic potential could be demonstrated in humans infected with GB-Virus C (GBV-C). In contrast, replicative GBV-C infection in HIV-infected individuals correlated with reduced progression to immunodeficiency (Tillmann, NEJM 2001). We therefore read with great interest, the article by Krajden et al. published recently in the International Journal of Cancer, in which the authors described a cohort of 553 patients with Non-Hodgkin lymphoma and 438 controls for evidence of serum GBV-C RNA. GBV-C RNA was found in 4.5% of NHL patients and in 1.8% of controls, a difference which under analysis achieved statistical significance (odds ratio 1⁄4 2.72, confidence interval1⁄4 1.22–6.69). This study however exclusively included apparently immunocompetent patients and therefore does not offer insight into the potential role of replicative GBV-C infection contributing to the preexisting increased risk of lymphoma in HIVinfected patients. To further clarify the prevalence of GBV-C infection in our cohort of HIV-infected patients with and without lymphoma, we performed a retrospective analysis. In total 33 HIV-positive patients with lymphoma were recruited from the HIV-outpatient clinic at Hanover Medical University for GBV-C RNA and the frequency of viremia was compared with 584 HIV-infected patients without lymphoma. From the 33 patients in the lymphoma group with a mean CD4þ T cell count of 371/lL (range 7–970 cells/lL) 7 had Hodgkin Lymphoma (HL) and 26 Non-Hodgkin Lymphoma (NHL). In total ten patients (30.3%) tested GBV-CRNA positive. In our control group 138 of 584 HIV-positive patients tested positive for GBV-C-RNA (23.6%). These results however failed to achieve statistical significance regarding an association between positive GBV-C-Status and lymphoma (p 1⁄4 0.39). Interestingly the updated results in our cohort revealed an increase in the overall incidence of GBV-C viremia from 16.8% (Tillmann et al. 2001) to 23.6%. This might indicate a general spread of GBV-C infection in our cohort with known elevated risks for parenteral or mucosal transmission of viral infections. Hence the elevated GBV-C incidence in lymphoma patients, described by Krajden et al. could be explained and a confounding phenomenon indicating elevated risks for transmission of other hypothetically oncogenic viruses. On the other hand, the persistence of GBV-C viremia in HIV-positive individuals has been explained by the prevalence of T-cellular immunodeficiency. Therefore it cannot be ruled out that an elevated incidence of GBV-C replication in lymphoma patients rather indicates a secondary or preexisting alteration of T-cell immunity than a causal factor for tumor ontogenesis. Yours sincerely, Diana Ernst Sven Pischke Mark Greer Heiner Wedemeyer Matthias Stoll

GB virus C coinfection in advanced HIV type-1 disease is associated with low CCR5 and CXCR4 surface expression on CD4+ T-cells

Coinfection with the flavivirus GB virus C (GBV-C) is frequent in patients suffering from HIV type-1 (HIV-1) infection because of shared routes of transmission. GBV-C coinfection has been proposed to exert a beneficial influence on HIV-1 infection. In vitro studies demonstrated down-regulation of C-C chemokine receptor type 5 (CCR5) as a potential mechanism by which GBV-C modulates HIV-1 disease progression. We therefore studied surface expression of the two major HIV-1 coreceptors, CCR5 and CXC chemokine receptor type 4 (CXCR4), on CD4(+) and CD8(+) T-cells in 128 HIV-1-positive patients stratified with respect to their GBV-C status, immune function and highly active antiretroviral therapy (HAART) status in vivo. GBV-C infection was studied in 128 HIV-1-infected patients by nested reverse transcriptase PCR. Fluorescence-activated cell sorting analysis was used to measure CCR5 and CXCR4 surface expression on CD4(+) and CD8(+) T-cells. GBV-C RNA replication was detected in 30% (38/128) of patients. In HIV-1-positive patients with advanced immunodeficiency, we found up-regulation of CCR5 surface expression on CD4(+) T-cells; however, in patients with GBV-C coinfection, no up-regulation of CCR5 CD4(+) T-cells was detected. Furthermore, CXCR4 surface expression was reduced in GBV-C-coinfected patients. These findings were independent of HAART status and HIV-1 viral load. HIV-1 coreceptor expression on CD8(+) T-cells was not altered in patients with GBV-C coinfection. GBV-C coinfection in HIV-1 disease leads to reduced expression of the two major HIV-1 coreceptors, CCR5 and CXCR4, on CD4(+) T-cells in patients at an advanced stage of immunodeficiency, providing a possible molecular explanation for the clinical benefit of GBV-C coinfection in late-stage HIV-1 disease.

GB virus C genotype 2 predominance in a hepatitis C virus/HIV infected population associated with reduced liver disease

GB virus C (GBV-C) infection in hepatitis C virus (HCV)/HIV co-infection is associated with a significant reduction in the severity of HCV-related liver disease. The role of GBV-C genotype in this association is unknown. It has been suggested that GBV-C genotype may influence CD4 positive T-cell counts in HCV/HIV co-infected patients. The aim of the present study was to identify the GBV-C genotype in a HCV/HIV co-infected population and determine if the GBV-C genotype contributes to a reduction in HCV-related liver disease. GBV-C RNA from 57 patients who were co-infected with HCV/HIV was analyzed. GBV-C RNA was detected by reverse transcription-polymerase chain reaction with primers to the NS5B gene and genotype determined by phylogenetic analysis after sequencing using E2 gene primers. Genotype 2 was the predominant isolate in our population and was detected in 50/56 (89.3%) of patients, although sequences with similarity to genotypes 1, 3, 4 and 5 were also identified. There was no statistical difference between CD4 positive T-cell counts in the GBV-C genotype 2 and non-genotype 2 groups. The GBV-C genotype distribution in our HCV/HIV patient group was consistent with that reported in other developed countries. The predominance of genotype 2 in this study meant that we could not draw a conclusion for the role of GBV-C genotype in the reduced severity of liver disease in co-infected patients but CD4 positive T-cell counts appeared to be unaffected by GBV-C genotype.

Mother‐to‐Child Transmission of GB Virus C in a Cohort of Women Coinfected with GB Virus C and HIV in Bangkok, Thailand

GB virus C (GBV-C) is an apathogenic virus that inhibits human immunodeficiency virus (HIV) replication in vitro. Mother-to-child transmission (MTCT) of GBV-C has been observed in multiple small studies. Our study examined the rate and correlates of MTCT of GBV-C in a large cohort of GBV-C-HIV-coinfected pregnant women in Thailand. Maternal delivery plasma specimens from 245 GBV-C-HIV-infected women and specimens from their infants at 4 or 6 months of age were tested for GBV-C RNA. Associations with MTCT of GBV-C were examined using logistic regression. One hundred one (41%) of 245 infants acquired GBV-C infection. MTCT of GBV-C was independently associated with maternal antiretroviral therapy (adjusted odds ratio [AOR], 5.21 [95% confidence interval {CI}, 2.12-12.81]), infant HIV infection (AOR, 0.05 [95% CI, 0.01-0.26]), maternal GBV-C load (8.0 log(10) copies/mL: AOR, 86.77 [95% CI, 15.27-481.70]; 7.0-7.9 log(10) copies/mL: AOR, 45.62 [95% CI, 8.41-247.51]; 5.0-6.9 log(10) copies/mL: AOR, 9.07 [95% CI, 1.85-44.33]: reference, <5 log(10) viral copies/mL), and caesarean delivery (AOR, 0.26 [95% CI, 0.12-0.59]). Associations with maternal GBV-C load and mode of delivery suggest transmission during pregnancy and delivery. Despite mode of delivery being a common risk factor for virus transmission, GBV-C and HIV were rarely cotransmitted. The mechanisms by which maternal receipt of antiretroviral therapy might increase MTCT of GBV-C are unknown.

GB virus C infection in pregnancy: Maternal and perinatal importance of the infection

Objectives The more effective way of transmission of GB virus C (GBV-C) is parenteral, but sexual and vertical transmission seem to be the main way of spreading. We evaluated the prevalence and the effect of GBV-C infection on pregnant women, vertical transmission and viral effects on the newborn. Study design This study has consecutively enrolled 879 pregnant women. All patients had blood sampling to determine GBV-C RNA, serologic tests for chronic viral infections and seric tests of hepatic damage. The newborns from infected mothers had blood sampling to detect the presence of GBV-C at birth, and after 3 and 6 months. Positive babies were checked until 18 months. Results 36 (4.1%) women resulted GBV-C positive. Among the positive patients none presented complications during pregnancy. Neither embryonic-fetal abnormalities nor relevant differences in fetal birth weight and week of gestation at delivery were found. 20 out of 36 babies had a follow-up. At birth, 13 (65%) babies were positive. 4 out of 9 vaginal deliveries (44%) and 9 out of 11 cesarean sections (82%) resulted positive to GBV-C RNA. The risk of GBV-C vertical transmission was not significantly increased by type of delivery ( p = 0.274). At 3 months, 13 babies were GBV-C positive (65%) and 7 were negative (35%). At the end of the follow-up, 9 babies were positive (45%), while 11 were negative (55%). Conclusion The percentage of patients positive to GBV-C RNA was comparatively high (4.1%). This prevalence, in a population without particular risk factors, confirms that common ways of transmission, such as the sexual and vertical ones, might have an important role in viral diffusion. Our data suggest that the infection does not influence the course of pregnancy. The rate of transmission found in our study is high. Type of delivery does not seem to be actually involved in vertical transmission and the protective role of cesarean section has not been confirmed.