GB virus C: the good boy virus?

Abstract

GB virus C (GBV-C) is a lymphotropic human virus discovered in 1995 that is related to hepatitis C virus (HCV). GBV-C infection has not been convincingly associated with any disease; however, several studies found an association between persistent GBV-C infection and improved survival in HIV-positive individuals. GBV-C infection modestly alters T cell homeostasis in vivo through various mechanisms, including modulation of chemokine and cytokine release and receptor expression, and by diminution of T cell activation, proliferation and apoptosis, all of which may contribute to improved HIV clinical outcomes. In vitro studies confirm these clinical observations and demonstrate an anti-HIV replication effect of GBV-C. This review summarizes existing data on potential mechanisms by which GBV-C interferes with HIV, and the research needed to capitalize on this epidemiological observation.

Figure 1

In vitro effects of GB virus C (GBV-C) proteins E2 and NS5A on CD4⁺ T cells. The E2 protein interferes with HIV cellular binding and/or fusion (purple box), whereas the NS5A protein downregulates CD4 and CXCR4 expression and induces SDF-1, the soluble ligand for CXCR4. NS5A protein also induces Th1 cytokines and blocks expression of Th2 cytokines (blue boxes). GBV-C E2 and NS5A proteins inhibit HIV replication (green box).

Figure 2

In vivo effects of GB virus C (GBV-C) infection that can potentially interfere with HIV replication. GBV-C infection reduces CXCR4 and CCR5 surface expression and induces soluble ligands for CCR5 (RANTES, MIP-1α, and MIP-1β) and CXCR4 (SDF-1). GBV-C infection reduces activation, proliferation and apoptosis in T cells. GBV-C also enhances expression of interferons, activates plasmacytoid dendritic cells and promotes Th1 cytokines leading to an enhanced innate immune response. These effects can potentially limit HIV replication and slow disease progression.