Immune escape of γ-herpesviruses from adaptive immunity

Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are two -herpesviruses identified in humans and are strongly associated with the development of malignancies. Murine -herpesvirus (MHV-68) is a naturally occurring rodent pathogen, representing a unique experimental model for dissecting -herpesvirus infection and the immune response. These -herpesviruses actively antagonize the innate and adaptive antiviral responses, thereby efficiently establishing latent or persistent infections and even promoting development of malignancies. In this review, we summarize immune evasion strategies of -herpesviruses. These include suppression of MHC-I-restricted and MHC-II-restricted antigen presentation, impairment of dendritic cell functions, downregulation of costimulatory molecules, activation of virus-specific regulatory T cells, and induction of inhibitory cytokines. There is a focus on how both -herpesvirus-derived and host-derived immunomodulators interfere with adaptive antiviral immunity. Understanding immune-evasive mechanisms is essential for developing future immunotherapies against EBV-driven and KSHV-driven tumors. Copyright (c) 2014 John Wiley & Sons, Ltd.