Role of GB virus C in modulating HIV disease

Abstract

GB virus C (GBV-C) is a member of the Flaviviridae family and the most closely related human virus to HCV. However, GBV-C does not replicate in hepatocytes, but rather in lymphocytes. GBV-C has a worldwide distribution and is transmitted sexually, parenterally and through mother-to-child transmission. Thus, co-infection with HCV and HIV is common. Until now, no human disease has been associated with GBV-C infection. However, there are several reports of a beneficial effect of GBV-C on HIV disease progression in vivo. Different mechanisms to explain these observations have been proposed, including modification of antiviral cytokine production, HIV co-receptor expression, direct inhibition of HIV-1 entry, T-cell activation and Fas-mediated apoptosis. Further understanding of these mechanisms may open new strategies for the treatment of HIV/AIDS.

Use of Flaviviral genetic fragments as a potential prevention strategy for HIV-1 Silencing

“…HIV-1/GBV-C co-infected individuals display higher CD4+ T cell counts, lower mortality rate, slower progression to AIDS and survive three times longer than HIV-1 monoinfected individuals [3,26,27]. Researchers debate whether the beneficial effects of coinfection of GBV-C in HIV-1-infected individuals are due to GBV-C viremia, or rather the presence of GBV-C anti-E2 antibodies or GBV-C NS5 antigen [3,5,27]. Previously, we demonstrated that the observed beneficial effects are due to modulation of the miRNAs in the coinfected host cells influencing the intracellular defense system [3,27].…”

“…miRNAs present a powerful forward genetics approach to dissect virus-host cell interactions [4][5][6]. By using human genome-wide miRNA multi-genome alignments we identified a total of 76 human miRNAs that can potentially silence HIV-1 at different stages of the viral life cycle.…”

“…Clinical reports indicate that GBV-C and some other members of the Flaviviridae infections are able to quell HIV-1 replication [3][4][5][6][8][9][10][11][12]25,27]. Our computational analyses, which show that a large number of mutually homologous miRNAs are present that may quell HIV-1, suggest that the mechanisms of the beneficial effects of the Flaviviridae co-infection against HIV-1 likely is via miRNAs and other mechanisms reported by various investigators may be of secondary nature, as has been previously reviewed [5][6][8][9][10][11][12]25,27]. If the hypothesis of extracellular structural mimicry is correct, then HIV-1 and GBV-C protein structures must show some degree of mutual homology.…”

“…[1,2]. However, certain co-infections may sometimes have beneficial effects [3][4][5]. Several reports have documented the favorable properties of flaviviral coinfection [3][4][5].…”

“…However, certain co-infections may sometimes have beneficial effects [3][4][5]. Several reports have documented the favorable properties of flaviviral coinfection [3][4][5]. Currently, the Flaviviridae is divided into four genera: Flavivirus, that includes WNV, DV and YFV; Hepacivirus that includes hepatitis C viruses, which are divided into six types, A, B, C, D, E and G; Pestivirus that includes swine fever virus (SFV) and bovine diarrhea virus (BDV); and the newly-designated Pegivirus that includes GBV-A, B and C in humans and GBV-Ccpz in the chimpanzee [6].…”