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

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.