Reversal of Immunity After Clearance of Chronic HCV Infection-All Reset?

Abstract

Chronic viral infections cause deterioration of our immune system. However, since persistent infections rarely can be eliminated, the reinvigoration capacity of an exhausted immune system has remained largely elusive. Chronic hepatitis C virus (HCV) infection can since some years be effectively cured with novel direct acting antiviral agents. Thus, it is now possible to study reversal of immunity in patients that are cured from a long-lasting chronic infection. We here highlight recent developments in the analysis of various immune cell populations during and after clearance of HCV infection. Surprisingly, whereas reinvigoration of certain immune traits clearly can be seen, many features of immune exhaustion persist over time after viral elimination. Thus, a long-term chronic insult might result in irreversible damage to our immune system. This will be important to consider in therapeutic vaccination efforts against chronic infection and in the development of immunotherapy based strategies against cancer.

Keywords: MAIT cell; T cell; chronic infection; direct acting antivirals; hepatitis C; natural killer cell; soluble inflammatory mediators.

Figure 1

Schematic illustration of immune cell function before and after elimination of chronic HCV infection. (A) Examples of possible immune exhaustion as a consequence of chronic HCV infection. (B) Time course for studying the impact of HCV clearance on immune cells. (C) Modulation of immunity after viral clearance with the degree of change ranging from (+/−) to (+++).