Carriage of GB Virus C/Hepatitis G Virus RNA Is Associated with a Slower Immunologic, Virologic, and Clinical Progression of Human Immunodeficiency Virus Disease in Coinfected Persons

Lefrère, Jean‐Jacques; Roudot‐Thoraval, Françoise; Morand‐Joubert, Laurence; Petit, Jean‐Claude; Lerable, Joëlle; Thauvin, M; Mariotti, Martine

doi:10.1086/314671

Cited by 139 publications

(112 citation statements)

References 29 publications

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“…In immunocompetent individuals GBV-C viremia is mostly cleared within the first years concomitantly by the development of antibodies directed against the envelope glycoprotein E2. GBV-C became of interest because several epidemiological studies demonstrated that coinfection of HIV-1 and GBV-C is associated with a slower progression to AIDS and prolonged survival (18,31,33,36,39). In contrast, other groups could not confirm the positive effect of GBV-C infection for HIV-infected individuals (3,4,32).…”

Section: Gb Virus C (Gbv-c) a Positive-strand Rna Virus Of The Flavimentioning

confidence: 99%

Peptides Derived from a Distinct Region of GB Virus C Glycoprotein E2 Mediate Strain-Specific HIV-1 Entry Inhibition

Koedel

Eissmann

Wend

et al. 2011

J Virol

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The nonpathogenic human GB virus C (GBV-C), a member of the Flaviviridae, is highly prevalent in individuals with HIV-1 infections or with parenteral and sexual risk factors. Long-term GBV-C viremia has been associated with better survival or improved diagnosis in several epidemiological studies. In a previous study we reported that the E2 glycoprotein of GBV-C interferes with HIV-1 entry in vitro. To address the question what region of the E2 protein is involved in suppression of HIV-1 replication, we performed an E2-derived peptide scanning and determined the HIV-inhibitory activity of each peptide in HIV replication assays. We demonstrate here that peptides representing the N-terminal part of the E2 protein from amino acids (aa) 29 to 72 are able to inhibit efficiently HIV-1 replication in vitro. In particular, the peptides P6-2 (representing the E2-region from aa 45 to 64) and P4762 (aa 37 to 64) showed the highest potency in HIV replication assays performed on TZM-bl cells with 50% inhibitory concentrations between 0.1 and 2 M. However, primary HIV-1 isolates representing clades A to H showed a high variability in their sensitivity to E2 peptides. Pseudovirus inhibition assays revealed that the sensitivity is determined by the gp120/gp41 envelope proteins. Using HIV-1 BlaM-Vpr-based fusion assays, we demonstrate that the E2-derived peptides prevent HIV-1 binding or fusion, presumably via interaction with the HIV-1 particle. Together, these findings reveal a new mechanism of viral interference, suggesting that the envelope protein E2 of GBV-C target directly HIV-1 particles to avoid entry of these virions.

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Section: Gb Virus C (Gbv-c) a Positive-strand Rna Virus Of The Flavimentioning

confidence: 99%

Peptides Derived from a Distinct Region of GB Virus C Glycoprotein E2 Mediate Strain-Specific HIV-1 Entry Inhibition

Koedel

Eissmann

Wend

et al. 2011

J Virol

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“…The beneficial effect of the co-infection by the GBV-C/HGV in HIVinfected subjects has been under intense scrutiny and debate over the last few years, after the first demonstration of its protective role by several research groups around the world 6,9,21 . Several studies corroborated these findings 23 while a few others failed to substantiate them 22 .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of GBV-C / HVG viremia in HIV-infected women

Silva

Rodrigues

Campos

et al. 2012

Rev. Inst. Med. trop. S. Paulo

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SUMMARYThe present study aimed at standardizing a real-time quantitative polymerase chain reaction assay to evaluate the presence of GBV-C/HGV RNA. A "TaqMan" assay using primers and probe derived from the 5′ NCR region was developed and validated. Two hundred and fifty-three plasma samples from HIV-infected women were tested for GBV-C viremia and antibody against the envelope protein 2. GBV-C RNA was detected in 22.5% of the patients whereas the antibody was identified in 25.3% of the cohort. Detection of viral RNA and of antibodies was mutually exclusive. Viral loads showed a mean of 1,777 arbitrary units / mL, being 1.1 and 13,625 arbitrary units / mL respectively the lowest and highest values measured. We conclude that the real-time quantitative polymerase chain reaction method developed is appropriate for the investigation of GBV-C RNA since it was shown to be highly specific and sensitive, as well as requiring few steps, preventing contamination and providing additional information as to the relative viremia of carriers, a parameter that must be included in studies evaluating the co-factors influencing the clinical outcome of HIV/AIDS.

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“…Active viremia with GBV-C has been detected by reverse transcription (RT)-PCR methods in 17% (9) to 43% (20) of HIV-positive individuals. In several, though not all, studies, HIV-infected people who were coinfected with GBV-C had decreased mortality (9,14,30,33,36,37) and favorable clinical markers of HIV disease progression (30,33,37) compared to those without GBV-C viremia. A meta-analysis found a highly significant association with prolonged survival in HIV-infected individuals when GBV-C RNA was detected five or more years following HIV infection (39).…”

mentioning

confidence: 99%

“…GBV-C viremia is measured by detecting viral RNA in serum or plasma using RT-PCR methods designed to amplify conserved sequences of the viral genome. Early studies of RT-PCR detection of GBV-C utilized primers that amplified the nonstructural-protein-coding regions 3 and 5A (NS3 and NS5A) (5, 12, 15); however, most subsequent studies have used primers that amplified the conserved 5Ј nontranslated region (5Ј NTR) of the genome (6,9,14,21,36,37). We previously designed primers to amplify two regions of the 5Ј NTR, the 3Ј nontranslated region, the two envelope glycoprotein-coding regions (E1 and E2), and five nonstructural-protein-coding regions (NS2, NS3, NS4, NS5A, and NS5B) (J. Xiang, F. LaBrecque, W. N. Schmidt, D. Klinzman, D. Brashear, D. R. LaBrecque, M. J. Perino-Phillips, and J. T. Stapleton, presented at the Tenth Triennial International Symposium on Viral Hepatitis and Liver Disease, 9 to 14 April 2000, Atlanta, GA).…”

mentioning

confidence: 99%

Effect of Primer Selection on Estimates of GB Virus C (GBV-C) Prevalence and Response to Antiretroviral Therapy for Optimal Testing for GBV-C Viremia

et al. 2006

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GB virus C (GBV-C; also called hepatitis G virus) is a common cause of infection associated with prolonged survival among HIV-infected individuals.The prevalences of GBV-C viremia vary widely in different studies, and there has been poor agreement among different laboratories performing GBV-C RNA detection in quality control studies. To determine the optimal method of measuring GBV-C RNA in clinical samples, samples obtained from 939 HIV-infected subjects were studied using reverse transcription (RT)-PCR methods amplifying four separate regions of the GBV-C genome. Primers amplifying the E2 coding region were 100% specific; however, their sensitivity was only 76.6%. In contrast, primers amplifying three additional conserved regions of the GBV-C genome (the 5 nontranslated region and the nonstructural protein-coding regions 3 and 5A) were more sensitive but produced higher rates of false-positive results. Using low-specificity primer sets influenced the significance of association between GBV-C viremia and response to antiretroviral therapy. Using a quantitative GBV-C RNA method, the GBV-C RNA concentration did not correlate with baseline or set point HIV RNA levels; however, a correlation between negative, low, and high GBV-C RNA levels and increasing reduction in HIV RNA following antiretroviral therapy was observed. Subjects with both GBV-C E2 antibody and viremia had significantly lower GBV-C RNA levels than did viremic subjects without E2 antibody. These studies demonstrate that accurate detection of GBV-C RNA by nested RT-PCR requires the use of primers representing multiple genome regions. Analyses based on testing with single primers do not lead to reliable conclusions about the association between GBV-C infection and clinical outcomes.

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Carriage of GB Virus C/Hepatitis G Virus RNA Is Associated with a Slower Immunologic, Virologic, and Clinical Progression of Human Immunodeficiency Virus Disease in Coinfected Persons

Cited by 139 publications

References 29 publications

Peptides Derived from a Distinct Region of GB Virus C Glycoprotein E2 Mediate Strain-Specific HIV-1 Entry Inhibition

Peptides Derived from a Distinct Region of GB Virus C Glycoprotein E2 Mediate Strain-Specific HIV-1 Entry Inhibition

Evaluation of GBV-C / HVG viremia in HIV-infected women

Effect of Primer Selection on Estimates of GB Virus C (GBV-C) Prevalence and Response to Antiretroviral Therapy for Optimal Testing for GBV-C Viremia

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