Effect of Coinfection with GB Virus C on Survival among Patients with HIV Infection

Xiang, Jinhua; Wünschmann, Sabina; Diekema, Daniel J.; Klinzman, Donna; Patrick, Kevin D.; George, Sarah L.; Stapleton, Jack T.

doi:10.1056/nejmoa003364

Cited by 343 publications

(352 citation statements)

References 31 publications

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“…A B [3][4][5][15][16]. Both direct interference on HIV-l replication, such as inhibition ofHIV-I entry in target cells mediated by down-regulated CCR5 co-receptor expression (9,17), and indirect mechanisms, such as prolonged maintenance of an intact Thl cytokine profile (10) and an increased number of circulating "(8 T cells releasing antiviral cytokines (18)(19), have been proposed.…”

Section: Experiment) the Maturation State Ofdc Was Evaluated Using Amentioning

confidence: 99%

“…GBV-C co-infection has been recently proposed to have a beneficial effect on HIV disease course, since slower disease progression and enhanced survival has been observed in GBV-C-positive as compared to GBV-C-negative subjects (3)(4). Moreover, loss of GBV-C viremia has been shown to be closely related to increased mortality and progression to AIDS (5-6) In addition, GBV-C-positive patients show a better initial response to antiretroviral treatments (7) and longer maintenance of HIV suppression (8).…”

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confidence: 99%

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Activation of Interferon Response Genes and of Plasmacytoid Dendritic Cells in HIV-1 Positive Subjects with GB Virus C Co-Infection

Lalle

Sacchi

Abbate

et al. 2008

Int J Immunopathol Pharmacol

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GB virus C (GBV-C) coinfection has a protective role in Human Immunodeficiency Virus (HIV) infection, and increases the duration of suppression of HIV-1 viremia in patients under Highly Active Anti-Retroviral Therapy (HAART). Since innate antiviral response may be involved in the protection, we analyzed the possible role of GBV-C as activator of innate immunity. To this aim, we measured the extent of activation of the interferon (IFN) system and of circulating Dendritic Cells (DC) in vivo, and the ability of GBV-C to activate these functions in vitro. Activation of IFN system and of circulating DC was compared in GBV-positive and -negative HIV-1 co-infected patients with HAART-driven suppression of HIV-1 viremia. Endogenous levels of IFN-γ and RNA-dependent protein kinase (PKR) mRNA were significantly higher in peripheral blood mononuclear cells (PBMC) from GBV-C-positive when compared to GBV-C-negative patients. IFN-γ expression was correlated with all the Interferon response genes (IRGs) and with GBV-C viremia. The frequency of circulating plasmacytoid DC (pDC) expressing the CD80 activation marker was increased in GBV-C-positive patients, and was correlated with GBV-C viral load. In vitro experiments indicated that GBV-C is able to induce IFN-γ expression in PBMC. In addition, in PBMC cultures GBV-C induced an increase of CD80 expression by pDC, that was reduced by antibody to IFN-γ. Our data indicate that in HIV-positive patients GBV-C coinfection promotes the activation of IFN-γ and downstream IRG expression, as well as with the activation/maturation of circulating pDC. GBV-C-driven IFN-γ activation is, at least in part, responsible for the increased maturation of pDC. This crosstalk may suggest a role for GBV-C coinfection in boosting the innate antiviral response to HIV infection.

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Section: Experiment) the Maturation State Ofdc Was Evaluated Using Amentioning

confidence: 99%

mentioning

confidence: 99%

Activation of Interferon Response Genes and of Plasmacytoid Dendritic Cells in HIV-1 Positive Subjects with GB Virus C Co-Infection

Lalle

Sacchi

Abbate

et al. 2008

Int J Immunopathol Pharmacol

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“…In experimental studies, GBV-C infection of peripheral-blood mononuclear cells resulted in decreased replication of both clinical and laboratory HIV strains that use either CCR5 or CXCR4 as their co-receptor. GBV-C induces HIV inhibitory chemokines and reduces the expression of HIV co-receptor CCR5 in vitro, that could block or reduce the decline of CD4 counts, hence justifying the better prognosis 24,25 .…”

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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“…However, the pathogenic relevance of GBV-C, if any, remains unclear. It does not cause hepatitis but has been associated with prolonged survival in human immunodeficiency virus-infected individuals (62)(63)(64). Bovine viral diarrhea virus (BVDV) is the prototype pestivirus.…”

mentioning

confidence: 99%

Conserved Determinants for Membrane Association of Nonstructural Protein 5A fromHepatitis C Virus and Related Viruses

Brass

Pál

Sapay

et al. 2007

J Virol

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Nonstructural protein 5A (NS5A) is a membrane-associated essential component of the hepatitis C virus (HCV) replication complex. An N-terminal amphipathic alpha helix mediates in-plane membrane association of HCV NS5A and at the same time is likely involved in specific protein-protein interactions required for the assembly of a functional replication complex. The aim of this study was to identify the determinants for membrane association of NS5A from the related GB viruses and pestiviruses. Although primary amino acid sequences differed considerably, putative membrane anchor domains with amphipathic features were predicted in the N-terminal domains of NS5A proteins from these viruses. Confocal laser scanning microscopy, as well as membrane flotation analyses, demonstrated that NS5As from GB virus B (GBV-B), GBV-C, and bovine viral diarrhea virus, the prototype pestivirus, display membrane association characteristics very similar to those of HCV NS5A. The N-terminal 27 to 33 amino acid residues of these NS5A proteins were sufficient for membrane association. Circular dichroism analyses confirmed the capacity of these segments to fold into alpha helices upon association with lipid-like molecules. Despite structural conservation, only very limited exchanges with sequences from related viruses were tolerated in the context of functional HCV RNA replication, suggesting virus-specific interactions of these segments. In conclusion, membrane association of NS5A by an N-terminal amphipathic alpha helix is a feature shared by HCV and related members of the family Flaviviridae. This observation points to conserved roles of the N-terminal amphipathic alpha helices of NS5A in replication complex formation.The family Flaviviridae comprises the genera Flavirus, Hepacivirus, and Pestivirus, as well as the as-yet-unassigned GB virus A (GBV-A), GBV-B, and GBV-C. These enveloped positivestrand RNA viruses express their structural and nonstructural proteins via translation of a single long open reading frame (30). Hepatitis C virus (HCV) is the sole member of the genus Hepacivirus and a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, affecting an estimated 3% of the world's population (44). GB viruses and pestiviruses are more closely related to HCV than the classical flaviviruses. The availability of efficient cell culture systems and animal models makes these related viruses attractive in vitro and in vivo models for HCV. GBV-B, the closest relative of HCV, was recovered from a tamarin inoculated with blood from a surgeon suffering from acute hepatitis (16, 54) and causes acute and chronic hepatitis in New World monkeys, which are believed to represent the natural hosts (10). Subsequent attempts to isolate GBV-B sequences from humans have failed. By contrast, GBV-C persistently infects humans. However, the pathogenic relevance of GBV-C, if any, remains unclear. It does not cause hepatitis but has been associated with prolonged survival in human immunodeficiency virus-infected individuals (62-64). ...

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Effect of Coinfection with GB Virus C on Survival among Patients with HIV Infection

Abstract: GBV-C infection is common in people with HIV infection and is associated with significantly improved survival.

Cited by 343 publications

References 31 publications

Activation of Interferon Response Genes and of Plasmacytoid Dendritic Cells in HIV-1 Positive Subjects with GB Virus C Co-Infection

Activation of Interferon Response Genes and of Plasmacytoid Dendritic Cells in HIV-1 Positive Subjects with GB Virus C Co-Infection

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

Conserved Determinants for Membrane Association of Nonstructural Protein 5A fromHepatitis C Virus and Related Viruses

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