Other microbial components associated with hepatitis C virus infection: Their effects on interferon-α/ribavirin treatment

Abstract

The hepatic immune response in patients with hepatitis C virus (HCV) infection has been the object of intensive studies. In fact, HCV is a lymphotropic virus and CD81 acts as its co-receptor on CD4+, CD8+, CD19+, and CD56+ lymphocytes, respectively (Kronenberger et al., 2006). Generally, antigen (AG)-specific CD8+ cell cytotoxic response is very effective in viral clearance, being that this function is sustained by the intervention of CD4+ cells via release of interferon (IFN)-γ and interleukin (IL)-2, which expands the pool of T cytolitic cells (Jellison et al., 2005). Additionally, activated AG-specific CD8+ cells generate a pool of memory cells, which protect the host against subsequent infections (Jabbari & Harty, 2006). However, this seems not to be the case in HCV infection because of mutations within immunodominant CD8 epitopes, which allow HCV to escape from immunosurveillance (Chang, 1998; Urbani et al., 2005). On the other hand, early defects of CD8+ cell cytolytic function have been reported in HCV infection, even including the capacity of these cells to exert antiviral activity (Rehermann & Nascimbeni, 2005; Bowen & Walker, 2005). In fact, in this precocious phase, CD8+ T cells interacting with high avidity with AG-presenting cells (APCs) may undergo deletion or poor activation (Bowen et al., 2005). On the other hand, later in infection CD8+ cells activated by HCV in the lymph nodes (LN) may interact with lower avidity with APCs, thus leading to an ineffective viral clearance (Snyder et al., 2003). Taken together, these events seem to contribute to HCV disease chronicity. Conversely, CD4+ cells seem to be very active against some conserved protein epitopes of the HCV, and their response correlates with viral clearance (Harcourt et al., 2004). Either in HCV-infected patients or in HCV-infected chimpanzees (Shoukry et al., 2004), production of IFN-γ from T helper(h)-1 cells is associated with a rapid clearance of circulating HCV. © 2008 Springer Science+Business Media, LLC.