Hepatitis C Virus Genetic Variability, Human Immune Response, and Genome Polymorphisms: Which Is the Interplay?

Abstract

Hepatitis C virus (HCV) infection is the main cause of chronic hepatitis, affecting an estimated 150 million people worldwide. Initial exposure to HCV is most often followed by chronic hepatitis, with only a minority of individuals spontaneously clearing the virus. The induction of sustained and broadly directed HCV-specific CD4⁺ and CD8⁺ T cell responses, together with neutralizing antibodies (nAb), and specific genetic polymorphism have been associated with spontaneous resolution of the infection. However, due to its high variability, HCV is able to overwhelm the host immune response through the rapid acquisition of mutations in the epitopes targeted by T cells and neutralizing antibodies. In this context, immune-mediated pressure represents the main force in driving HCV evolution. This review summarizes the data on HCV diversity and the current state of knowledge about the contributions of antibodies, T cells, and host genetic polymorphism in driving HCV evolution in vivo.

Keywords: adaptive immune responses; clearance; genetics polymorphism; hepatitis C virus; immune escape; viral variability.

Figure 1

Diagrammatic representation of the 9.6 kb positive stranded RNA genome (top panel) and structural and non-structural proteins (lower panel).

Figure 2

Representation of the interferon lamda 3-4 (IFNL) locus and IFN 1 and two loci in chromosome 19q13 with key single nucleotide polymorphisms (SNPs) involved in clearance of HCV infection.