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ABSTRACT: Epidemiological studies have revealed an association between GB virus C (GBV-C) long-term viraemia and ameliorated HIV disease progression. We have provided evidence that a single protein of GBV-C, the glycoprotein E2, interferes with early HIV replication steps of both X4- and R5-tropic HIV strains. Preincubation with anti-E2 antibody specifically abrogates the inhibitory effect. Results were confirmed by the in-vitro expression of GBV-C E1/E2 encoding RNA.
AIDS 04/2007; 21(5):645-7. · 6.24 Impact Factor
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ABSTRACT: GB virus type C (GBV-C) is a human flavivirus that may cause persistent infection, although most infected individuals clear viremia and develop antibodies to the envelope glycoprotein E2. To study GBV-C E2 antigenicity and cell binding, murine anti-E2 monoclonal antibodies (MAbs) were evaluated to topologically map immunogenic sites on GBV-C E2 and for the ability to detect or block recombinant E2 binding to various cell lines. Five competition groups of MAbs were identified. Groups I and II did not compete with each other. Group III competed with both groups I and II. Group IV did not compete with group I, II, or III. One MAb competed with all of the other MAbs, suggesting that the epitopes bound by these MAbs are intimately related. Individually, none of the MAbs competed extensively with polyclonal human convalescent antibody (PcAb); however, combinations of all five MAb groups completely blocked PcAb binding to E2, suggesting that the epitopes bound by these MAbs form a single, immunodominant antigenic site. Only group I and III MAbs detected purified recombinant E2 bound to cells in binding assays. In contrast, group II MAbs neutralized the binding of E2 to cells. Both PcAb and MAbs were conformation dependent, with the exception of one group II MAb (M6). M6 bound to a five-amino-acid sequence on E2 if the peptide included four C-terminal or eight N-terminal residues, suggesting that the GBV-C E2 protein contains a single immunodominant antigenic site which includes a complex epitope that is involved in specific cellular binding.
Journal of Virology 01/2007; 80(24):12131-40. · 5.40 Impact Factor
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ABSTRACT: Persistent GB virus C (GBV-C) coinfection leads to slower human immunodeficiency virus (HIV) progression. Despite the existence of multiple GBV-C genotypes, their relevance to the progression of HIV disease is unknown. We therefore investigated (1) the prevalence and genotype of GBV-C in hepatitis C virus (HCV)/HIV-coinfected patients and (2) the impact of HCV treatment on GBV-C RNA clearance.
We retrospectively studied 130 HCV/HIV-coinfected patients initiating HCV therapy. Anti-E2 enzyme-linked immunosorbent assay, reverse-transcription polymerase chain reaction (PCR), and real-time PCR were used to detect and quantify GBV-C infection. GBV-C genotype was determined by sequencing the 5' untranslated region.
GBV-C infection (past or current) was identified in 111 (85%) of the patients. Ongoing GBV-C replication was detected in 40 patients. Coinfection with GBV-C genotype 2 was associated with significantly higher CD4(+) cell counts. After 24 weeks of HCV therapy, GBV-C RNA clearance was observed in 50% of patients, although this was not associated with changes in HIV load or with CD4(+) cell counts. Sustained GBV-C RNA clearance was observed in 31% of patients with GBV-C RNA detected at baseline.
GBV-C coinfection was extremely common. GBV-C RNA clearance with HCV therapy was associated with neither short-term loss of HIV control nor impaired immune status. The association of GBV-C genotype 2 with higher CD4(+) cell counts merits further study.
The Journal of Infectious Diseases 09/2006; 194(4):410-9. · 6.41 Impact Factor
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Susan Schuval,
Jane C Lindsey,
Jack T Stapleton,
Russell B Van Dyke,
Paul Palumbo,
Lynne M Mofenson,
James M Oleske,
Joseph Cervia,
Andrea Kovacs,
Wayne N Dankner, [......],
Gregory Ciupak,
Nancy Webb,
Michelle Eagle,
Dorothy Smith,
Roslyn Hennessey,
Melissa Goodman-Kerkau,
Donna Klinzman, Georg Hess,
Dietmar Zdunek,
Myron J Levin
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ABSTRACT: GB virus C (GBV-C) infection occurs in 20-40% of human immunodeficiency virus (HIV)-infected adults, and coinfection is associated with improved HIV disease outcome.
To determine the prevalence of GBV-C infection in children who were perinatally infected with HIV, we conducted a cross-sectional prevalence survey in a cohort of perinatally infected HIV-positive children selected from a large, multicenter observational protocol. A blood specimen was obtained and tested for GBV-C viremia with the use of a qualitative GBV-C RNA assay and screened for past GBV-C infection with enzyme-linked immunosorbent assay to detect antibodies to the GBV-C envelope protein E2 (E2 Ab).
The 354 children who participated in the substudy were relatively healthy, with a median CD4 of 784 cells/mm and median HIV-1 viral load of 1055 copies/mL. The prevalence of GBV-C viremia was 20 of 353 or 5.7% (95% confidence interval, 3.5-8.6%), and the prevalence of E2 Ab was 12 of 354 or 3.4% (95% confidence interval, 1.8-5.8%). GBV-C viremic patients were older than patients without past GBV-C infection (median age, 12.8 years versus 10.7 years). Median CD4 lymphocyte counts were highest in subjects without GBV-C infection and lowest in those with E2 Ab.
GBV-C prevalence rates are lower in children with perinatal HIV infection than those reported for HIV-infected adults. With the exception of evidence that GBV-C viremic children had lower rates of Centers for Disease Control and Prevention HIV disease category C disease before GBV-C testing, we did not find evidence of improved HIV disease outcome in coinfected patients, but the number of HIV/GBV-C-coinfected children was small.
The Pediatric Infectious Disease Journal 06/2005; 24(5):417-22. · 3.58 Impact Factor
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Carolyn F Williams,
Donna Klinzman,
Traci E Yamashita,
Jinhua Xiang,
Philip M Polgreen,
Charles Rinaldo,
Chenglong Liu,
John Phair,
Joseph B Margolick,
Dietmar Zdunek, Georg Hess,
Jack T Stapleton
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ABSTRACT: GB virus C (GBV-C), which is not known to be pathogenic in humans, replicates in lymphocytes, inhibits the replication of human immunodeficiency virus (HIV) in vitro, and has been associated with a decreased risk of death among HIV-positive persons in some, but not all, studies. Previous studies did not control for differences in the duration of HIV or GBV-C infection.
We evaluated 271 men who were participants in the Multicenter Acquired Immunodeficiency Syndrome Cohort Study for GBV-C viremia (by means of a reverse-transcriptase-polymerase-chain-reaction assay) or E2 antibody (by means of an enzyme-linked immunosorbent assay) 12 to 18 months after seroconversion to positivity for HIV (the early visit); a subgroup of 138 patients was also evaluated 5 to 6 years after HIV seroconversion (the late visit).
GBV-C infection was detected in 85 percent of men with HIV seroconversion on the basis of the presence of E2 antibody (46 percent) or GBV-C RNA (39 percent). Only one man acquired GBV-C viremia between the early and the late visit, but 9 percent of men had clearance of GBV-C RNA between these visits. GBV-C status 12 to 18 months after HIV seroconversion was not significantly associated with survival; however, men without GBV-C RNA 5 to 6 years after HIV seroconversion were 2.78 times as likely to die as men with persistent GBV-C viremia (95 percent confidence interval, 1.34 to 5.76; P=0.006). The poorest prognosis was associated with the loss of GBV-C RNA (relative hazard for death as compared with men with persistent GBV-C RNA, 5.87; P=0.003).
GBV-C viremia was significantly associated with prolonged survival among HIV-positive men 5 to 6 years after HIV seroconversion, but not at 12 to 18 months, and the loss of GBV-C RNA by 5 to 6 years after HIV seroconversion was associated with the poorest prognosis. Understanding the mechanisms of interaction between GBV-C and HIV may provide insight into the progression of HIV disease.
New England Journal of Medicine 04/2004; 350(10):981-90. · 53.30 Impact Factor
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ABSTRACT: To determine whether GB virus C (GBV-C) infection is associated with protection against vertical transmission of human immunodeficiency virus (HIV), we tested 186 HIV-positive pregnant women for GBV-C. Neither active nor prior GBV-C infection was associated with a lower rate of HIV acquisition among infants. Thus, GBV-C does not appear to protect against perinatal HIV acquisition.
Clinical Infectious Diseases 04/2004; 38(6):e46-8. · 9.15 Impact Factor
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ABSTRACT: To study how GB virus C (GBV-C) coinfection affects the response to highly active antiretroviral therapy (HAART), 146 human immunodeficiency virus (HIV)-infected patients were tested for GBV-C RNA and antibodies against GBV-C E2 protein, and responses to HAART were evaluated. GBV-C-infected patients exhibited a complete virological response to HAART more often than patients without [correction] GBV-C and had a greater increase in median CD4 cell count and a marginally greater median HIV RNA level decrease. This association was found to be independent of baseline CD4 cell count and plasma HIV RNA, which indicates that an association exists between GBV-C infection and response to HAART.
The Journal of Infectious Diseases 03/2003; 187(3):504-7. · 6.41 Impact Factor
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Clinical Microbiology and Infection 05/1999; 5(4):236-237. · 4.54 Impact Factor
