Associations, Outcomes and Genomics of GB Virus C, Hepatitis C Virus and Human Immunodeficiency Virus Infection

Background and Research Plan:

GBV-C and hepatitis G virus (HGV) are both RNA viruses from the Flaviviridae family. Molecular characterization of these viruses has shown them to be virtually identical to each other (1,2). GBV-C was first isolated in 1995 from an archival blood sample obtained in the 1960s from a surgeon with acute non A-E hepatitis (3). GBV-C has a 29% amino acid sequence homology with Hepatitis C Virus (HCV), another flavivirus (4). However, GBV-C in contrast to HCV, is not hepatotropic as the virus neither replicates primarily in hepatocytes nor causes acute or chronic hepatitis. Indeed, GBV-C does not cause any specific disease nor does it represent a substantial health risk in humans. Nevertheless, GBV-C infection is relatively common with a 2% prevalence rate in healthy blood donors, the majority of whom clear the virus and develop antibodies to the envelope glycoprotein E2.

HIV infection has a particularly high rate of co-infection with GBV-C. Studies suggest that co-infection leads to a beneficial effect on the course of HIV (5,6,7) with co-infection associated with a significantly lower mortality rate among HIV-infected subjects compared to those not infected with GBV-C. The mechanism of the beneficial effect of GBV-C on the course of HIV infection is obscure.

Among new cases of non-A, non-B hepatitis in the United States, 18 percent are positive for GBV-C, and 80% of these patients are also infected with HCV. Amongst patients with HCV, 10-20% have GBV-C RNA in their serum (4). In another report 189 patients with chronic HCV infection were evaluated; 21 (11%) were positive for GBV-C RNA (8). The course of the HCV infection and the response to interferon-alfa were not affected by co-infection with GBV-C. Interferon-alfa led to a decrease in GBV-C RNA titers that was not sustained after the cessation of therapy. Similar findings were noted in another study in which liver biopsies were performed (9). Detailed histopathologic examination revealed no difference between the patients infected with HCV alone and the 15 percent who were co-infected with GBV-C. There have been no studies to date looking at the effect GBV-C, HCV and HIV have on each other.

Our previous studies into HIV and GBV-C have suggested that co-infection is common. Active GBV-C infection is frequently observed in persons involved in high-risk sexual activity and with HIV infection. Homosexual intercourse appears to be a more effective means of transmission of GBV-C. GBV-C has the same epidemiology and transmission as HIV and underlines the intimate association between GBV-C and HIV (10).