GB virus type C: a virus in search of a disease or a role in HIV therapy?

GB virus type C, first isolated in 1995, is a single-stranded RNA flavivirus that is genetically similar to hepatitis C virus (HCV) [1]. GBV-C is a relatively common infection worldwide, with up to 2% of blood donors and up to 40% of injection drug users (IDUs) in the United States demonstrating presence of GBV-C RNA in their plasma [1]. Up to 16% of healthy US blood donors and up to 70% of US IDUs have antibody to the E2 envelope protein (anti-E2), which is evidence of a prior infection with GBV-C [1]. Among infected individuals, there is a large range of levels of GBV-C viremia. Although, the level of viremia remains relatively constant in an individual and can persist for up to 16 years. Viremia eventually resolves in the majority of individuals, with the development of anti-E2 antibody which persists for life in most individuals [1, 2]. Current data suggest that the routes of transmission of HIV-1 and GBV-C are similar. In addition to the very high rate of transmission among IDUs, GBV-C transmission by blood product transfusion and organ transplantation have been well documented. GBV-C is also more efficiently transmitted through sexual exposure than is HCV. GBV-C transmission from infected mother to her child has also been well documented previously [3]. For the past decade, a number of studies have failed to support early suggestions that GBV-C may be associated with either chronic or acute liver disease [1, 4]. In fact, there is no convincing evidence that GBV-C infection causes any human pathology, leading Dickens [4] to suggest that it be renamed " human orphan flavivirus. " In 1998, as interest in GBV-C research was beginning to wane, initial reports suggesting that HIV-infected patients co-infected with GBV-C had slower disease progression were published [4]. Subsequently , a number of other studies have demonstrated an association between GBV-C infection and a higher CD4 count, a lower HIV plasma virus load, slower HIV disease progression, and an improved response to HAART [1, 5, 6]. In addition, an inverse correlation has been demonstrated between GBV-C load and HIV-1 load in coinfected individuals [6]. The proposed mechanisms for this interaction include GBV-C–mediated reduction of CCR5 expression, induction of anti-HIV chemokines, improved recognition of HIV-infected cells by cross-reactive anti– GBV-C cytolytic T lymphocytes, and alteration in cytokine response that results in a preservation of a TH1 immune response to HIV-1 infection [1, 7]. Like …