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.
Highlights
Chronic viral infections have a profound impact on the immune system
It is well established that patients with chronic hepatitis viruses and/or HIV infection have an impaired adaptive immunity with dysfunctional CD4+ and CD8+ T cells contributing to the inability to clear the infection [1, 2]
In a recent study the data suggested that CD8T cell memory was rather narrow after successful treatment with direct acting antiviral (DAA), and the authors suggested that vaccination maybe one option to induce the broader memory response which may provide protective immunity [63]
Summary
Chronic viral infections have a profound impact on the immune system. In humans, it is well established that patients with chronic hepatitis viruses and/or HIV infection have an impaired adaptive immunity with dysfunctional CD4+ and CD8+ T cells contributing to the inability to clear the infection [1, 2]. EVIDENCE FOR REVERSAL OF IMMUNITY AFTER SUPPRESSION, BUT NOT CLEARANCE, OF A CHRONIC VIRAL INFECTION IN HUMANS It has been debated over the years to what extent the profound immune alterations observed in persistent infections could be reversed upon control or elimination of the underlying infection. This has been addressed to some extent in patients with chronic hepatitis B virus (HBV), hepatitis delta (HDV) or HIV infections receiving treatment. No full restoration of HIV-specific T cell responses was observed even after the virus had been suppressed for several years with antiviral treatment [13]. Evidence for partial reversal of immunity exists in studies of these infections, the full reinvigoration capacity of the immune system is not possible to gauge since the infections de facto are not eliminated
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