GB virus type C interactions with HIV: the role of envelope glycoproteins

Abstract

SUMMARY GB virus C/hepatitis G virus (GBV-C/HGV) is the most closely related human virus to hepatitis C virus (HCV). GBV-C is lymphotropic and not associated with any known disease, although it is associated with improved survival in HIV-infected individuals. In peripheral blood mononuclear cells, GBV-C induces the release of soluble ligands for HIV entry receptors (RANTES, MIP-1a, MIP-1b and SDF-1), suggesting that GBV-C may interact with lymphocytes to induce a chemokine and/or cytokine milieu that is inhibitory to HIV infection. Expression of GBV-C envelope glycoprotein E2 in CD4+ T cells or addition of recombinant E2 to CD4 cells recapitulates the HIV inhibition seen with GBV-C infection. Like HCV E2, GBV-C E2 is predicted to be post-translationally processed in the endoplasmic reticulum and is involved with cell binding. The C-termini of GBV-C E1 and E2 proteins contain predicted transmembrane domains sharing features with HCV TM domains. To date, cellular receptor(s) for GBV-C E2 have not been identified. GBV-C E2-mediated HIV inhibition is dose-dependent and HIV replication is blocked at the binding and/or entry step. In addition, a putative GBV-C E2 fusion peptide interferes with HIV gp41 peptide oligomerization required for HIV-1 fusion, further suggesting that GBV-C E2 may inhibit HIV entry. Additional work is needed to identify the GBV-C E2 cellular receptor, characterize GBV-C E2 domains responsible for HIV inhibition, and to examine GBV-C E2-mediated fusion in the context of the entire envelope protein or viral-particles. Understanding the mechanisms of action may identify novel approaches to HIV therapy.

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

“…The prevalence of GBV-C RNA in the HIV-infected population is much higher than that observed in healthy subjects, with greater geographical variations. In Brazil we and others described a prevalence close to 10% among blood donors 2,11 while in Europe and North America a prevalence of 1-4% was verified 15 . In contrast, 14-43% of HIV-infected subjects harbor the viral RNA.…”

“…GBV-C is prevalent worldwide in healthy populations such as blood donors but also in specific groups of patients like HIV-infected subjects (reviewed in 15 ). It is transmitted mainly by sexual contact but also parenterally, which explains the high prevalence found in intravenous drug users and patients submitted to multiple transfusions 16 .…”

Tropism of human pegivirus (formerly known as GB virus C/hepatitis G virus) and host immunomodulation: insights into a highly successful viral infection

“…Although HPgV has not been conclusively shown to cause any human disease (Bhattarai & Stapleton, 2012;Mohr & Stapleton, 2009), several studies observed an association between HPgV viraemia and an increased risk of non-Hodgkin's lymphoma (Chang et al, 2014; Civardi et al, 1998;De Renzo et al, 2002;Ellenrieder et al, 1998;Giannoulis et al, 2004 , 1997). In contrast, HPgV is associated with a beneficial effect in human immunodeficiency virus (HIV) infection, and most studies and a meta-analysis found prolonged survival in HIV-infected individuals co-infected with HPgV compared with those without HPgV viraemia Nunnari et al, 2003;Tillmann et al, 2001;Toyoda et al, 1998;Williams et al, 2004;Xiang et al, 2001;Zhang et al, 2006).…”

“…The prevalence of HPgV viraemia in cross-sectional serum surveys of healthy blood donors in developed countries is between 1 and 5 %, whilst up to 20 % of blood donors in developing countries have active infection (Mohr & Stapleton, 2009). The rate of HPgV viraemia is also higher amongst individuals with blood-borne or sexually transmitted infections.…”

“…Thus, antibody to E2 represents a marker of prior infection, although antibody levels may decrease and become undetectable over time (Gutierrez et al, 1997;Tacke et al, 1997;Tanaka et al, 1998a). As 12-20 % of blood donors from developed countries have HPgV E2 antibodies (Gutierrez et al, 1997;Tacke et al, 1997) and a higher percentage of healthy blood donors in developing countries have E2 antibodies (reviewed by Mohr & Stapleton, 2009), the data suggest that~1.5-2.5 billion people are currently infected or have evidence of prior HPgV infection, making this virus a major contributor to the human virome. Thus, HPgV shares infection rates with many viruses, including papillomaviruses, herpesviruses and torque teno viruses (TTVs), frequently found in healthy individuals (Okamoto, 2009).…”