T cell responses during HBV and HCV infections: similar but not quite the same?

Abstract

The hepatitis B and C viruses persist by evasion of T cell immunity. Persistence depends upon premature failure of CD4+ T cell help and loss of CD8+ T cell control because of epitope mutational escape and/or functional exhaustion. Powerful new immunological and transcriptomic tools provide insight into the mechanisms of T cell silencing by HBV and HCV. Similarities are apparent, including dysregulated expression of common inhibitory/immune checkpoint receptors and transcription factors. There are also differences. T cell exhaustion is uniform in HCV infection, but varies in HBV infection depending on disease stage and/or protein target. Here, we review recent advances defining similarities and differences in T cell evasion by HBV and HCV, and the potential for reversal following antiviral therapy.

Figure 1

CD4+ and CD8+ T cell similarities and differences in during chronic HBV and HCV infection. HBV and HCV-specific CD8+ T cells transition from a memory-like state to an exhausted state during chronic infection (indicated by arrows). HBV-specific CD8+ T cells are more heterogeneous in phenotype and function as the transition between states may be modifed by disease stage (orange arrow) and HBV protein (green arrow). There are no known modifiers of this transition in chronic HCV infection (purple arrow) and CD8+ T cell heterogeneity is not as apparent.