Adaptive Immune Response against Hepatitis C Virus

Abstract

A functional adaptive immune response is the major determinant for clearance of hepatitis C virus (HCV) infection. However, in the majority of patients, this response fails and persistent infection evolves. Here, we dissect the HCV-specific key players of adaptive immunity, namely B cells and T cells, and describe factors that affect infection outcome. Once chronic infection is established, continuous exposure to HCV antigens affects functionality, phenotype, transcriptional program, metabolism, and the epigenetics of the adaptive immune cells. In addition, viral escape mutations contribute to the failure of adaptive antiviral immunity. Direct-acting antivirals (DAA) can mediate HCV clearance in almost all patients with chronic HCV infection, however, defects in adaptive immune cell populations remain, only limited functional memory is obtained and reinfection of cured individuals is possible. Thus, to avoid potential reinfection and achieve global elimination of HCV infections, a prophylactic vaccine is needed. Recent vaccine trials could induce HCV-specific immunity but failed to protect from persistent infection. Thus, lessons from natural protection from persistent infection, DAA-mediated cure, and non-protective vaccination trials might lead the way to successful vaccination strategies in the future.

Phylogenetic analysis in the clinical risk management of an outbreak of hepatitis C virus infection among transfused thalassaemia patients in Italy

“…This observation confirms previously published data demonstrating the possibility of reinfection both in patients who have recovered spontaneously from HCV infection [6] and in patients who have achieved a sustained virological response after antiviral therapy [23,24]. In fact, some defects in adaptive immune cell populations in patients with HCV infection can restrict themselves in obtaining only a limited functional memory and allowing the reinfection of cured individuals [25].…”

CD8+ T Cell Responses during HCV Infection and HCC

“…Furthermore, CD8 + T cell depletion studies conducted in chimpanzees resulted in prolonged viremia, further highlighting the central antiviral role of CD8+ T cells [ 36 ]. The central role of CD8 + T cell responses is also supported by the observed protective effects of diverse human leukocyte antigen class I alleles, such as HLA-B*27 or –A*03 [ 39 ]. Virus-specific CD8 + T cells that are associated with HCV clearance in humans are characterized by expression of activation-associated molecules (PD-1, CD39) [ 38 , 40 ], high levels of T-bet [ 41 ], and a low cytokine production [ 37 ].…”

Adaptive Immune Responses, Immune Escape and Immune-Mediated Pathogenesis during HDV Infection

“…This includes the loss of versatile cytokine production and proliferation, impaired cytotoxicity and the expression of inhibitory receptors, in particular, PD-1, CD160, 2B4, Tim-3, and CD39, as well as the upregulation of specific transcription factors, such as TOX [124][125][126][127][128]. In chronic HCV infection, virus-specific CD8+ T cells that target conserved (non-escaped) epitopes display a rather exhausted phenotype, while CD8+ T cells targeting escaped epitopes display a more memory-like phenotype [111,129]. The role of T cell exhaustion in chronic HBV infection is a current research focus and might depend on the targeted antigen [126,[130][131][132].…”