Immune responses during acute and chronic infection with hepatitis C virus

Abstract

Hepatitis C virus (HCV) induces persistent infection and causes chronic liver disease in most infected patients. Vigorous HCV-specific CD4+ and CD8+ T cell responses against HCV multiple epitopes are necessary for spontaneous viral clearance during the acute phase, but the virus appears to have multiple strategies to evade these defenses. There are relatively few studies on the role of immune responses during the chronic phase of infection. CD4+ T cell responses appear to protect against liver injury and may be important to clearance during interferon and ribavirin based therapy. Classic cytotoxic T cells (CTL) may primarily damage the liver in chronic HCV, but there may be subpopulations of T cells that protect against liver inflammation. Resolution of these outstanding questions is important to the development of a prophylactic vaccine as well as improving therapeutic options for those with chronic infection.

Calpain activation by hepatitis C virus proteins inhibits the extrinsic apoptotic signaling pathway

“…HCV is particularly successful in avoiding elimination: it is estimated that up to 80% of acute infections progress to chronicity. 1 On top of several mechanisms of interference with the type 1 interferon production and response, antigen presentation, and cellmediated immune response, 23,24 HCV also modulates ap- optosis of the infected cell. 25 We previously reported that the HCV viral proteins decrease the expression of the proapoptotic protein Bid.…”

Inflammatory Biomarkers and Liver Histopathology in Non-Uremic and Uremic Chronic Hepatitis C Patients

“…Inflammatory events play an important role during the course of chronic hepatitis C (cHepC) (8)(9)(10). Main contributors are cytokine producing CD4+ T and CD8+ T cell proliferation, increased CD5+ B cells, IL-2, IFN-γ and TNF α (8)(9)(10).…”

“…Main contributors are cytokine producing CD4+ T and CD8+ T cell proliferation, increased CD5+ B cells, IL-2, IFN-γ and TNF α (8)(9)(10). Neutrophil lymphocyte ratio (NLR) and thrombocyte lymphocyte ratio (PLR) are used as markers of inflammation in various diseases including atherosclerotic heart and renal disease.…”

Identification and retrospective validation of T-cell epitopes in the hepatitis C virus genotype 4 proteome

“…6,10 The cellular immune response occurs through the cytotoxic activity of CD8 + T cells on infected hepatocytes and the immuno-modulatory and antiviral cytokine-secreting actions of the CD4 + T cells. 7 Although spontaneous viral clearance is possible, in the majority of cases the virus succeeds in evading the immune response by several mechanisms, leading to persistent infection. Chief among the evasion mechanisms is the highly mutable nature of the virus, which allows it to produce escape variants and evade recognition by cells of the adaptive immune system.…”

“…3,6 Following HCV infection of the liver, the host's innate immune system responds via the activation of natural killer lymphocytes and the production of type I and III interferons. [7][8][9] The adaptive humoral response involves the production of neutralizing antibodies that may block viral entry into healthy hepatocytes by targeting the viral envelope's structural proteins E1 and E2. 6,10 The cellular immune response occurs through the cytotoxic activity of CD8 + T cells on infected hepatocytes and the immuno-modulatory and antiviral cytokine-secreting actions of the CD4 + T cells.…”