Hepatitis C Virus-Mediated Modulation of Cellular Immunity

Abstract

The hepatitis C virus (HCV) is a major cause of chronic liver disease globally. A chronic infection can result in liver fibrosis, liver cirrhosis, hepatocellular carcinoma and liver failure in a significant ratio of the patients. About 170 million people are currently infected with HCV. Since 80 % of the infected patients develop a chronic infection, HCV has evolved sophisticated escape strategies to evade both the innate and the adaptive immune system. Thus, chronic hepatitis C is characterized by perturbations in the number, subset composition and/or functionality of natural killer cells, natural killer T cells, dendritic cells, macrophages and T cells. The balance between HCV-induced immune evasion and the antiviral immune response results in chronic liver inflammation and consequent immune-mediated liver injury. This review summarizes our current understanding of the HCV-mediated interference with cellular immunity and of the factors resulting in HCV persistence. A profound knowledge about the intrinsic properties of HCV and its effects on intrahepatic immunity is essential to be able to design effective immunotherapies against HCV such as therapeutic HCV vaccines.

Contribution of genes for killer cell immunoglobulin-like receptors (KIR) to the susceptibility to chronic hepatitis C virus infection and to viremia

“…Unique feature of NK cells are their receptors possessing various functions and ligands. The latter, often belonging to MHC group, may contribute to alterations in the immune response against viral antigens, either in augmentation or suppression and even tolerance [3,4]. Expression or absence of particular receptors on NK cells was found to influence the course of HCV infection.…”

“…HCV infection is controlled by both innate and adaptive immunity [3,4]. Natural killer (NK) cells are important element of innate immunity against viruses, although their numbers decrease in the liver during chronic HCV infection [5,6].…”

Killer Cell Immunoglobulin-Like Receptor Gene Associations with Autoimmune and Allergic Diseases, Recurrent Spontaneous Abortion, and Neoplasms

“…The protection from low-dose (injection or needle stick) but not from high-dose HCV infection was first described by Khakoo et al (2004) in British Caucasoids and Afroamericans. The regulation of HCV infection by NK cells was briefly reviewed recently by Brenndörfer and Sällberg (2012). …”

The Role of Chemokines in Hepatitis C Virus-Mediated Liver Disease

“…In chronic HCV infection, innate and adaptive immunity are impaired on many levels [36,37]. The HCV-mediated modulation of the chemokine response in the liver has implications for both viral persistence and the development of liver disease.…”