Exploiting human herpesvirus immune evasion for therapeutic gain: potential and pitfalls

Abstract

Herpesviruses stand out for their capacity to establish lifelong infections of immunocompetent hosts, generally without causing overt symptoms. Herpesviruses are equipped with sophisticated immune evasion strategies, allowing these viruses to persist for life despite the presence of a strong antiviral immune response. Although viral evasion tactics appear to target virtually any stage of the innate and adaptive host immune response, detailed knowledge is now available on the molecular mechanisms underlying herpesvirus obstruction of MHC class I-restricted antigen presentation to T cells. This opens the way for clinical application. Here, we review and discuss recent efforts to exploit human herpesvirus MHC class I evasion strategies for the rational design of novel strategies for vaccine development, cancer treatment, transplant protection and gene therapy.

Cyprinid Herpesvirus 3

“…Members of the Herpesviridae family have developed sophisticated immune evasion mechanisms (Horst, Ressing, & Wiertz, 2011). Bioinformatics analysis of the CyHV-3 genome revealed several genes encoding putative homologs of host or viral immunerelated genes (Aoki et al, 2007).…”

Immune Regulation and Evasion of Mammalian Host Cell Immunity During Viral Infection

“…They all produce infectious progenies by downregulating MHC-II expression without changing any Adenovirus also retains MHC-I molecules in ER [36,45,65,106]. The complex assembly of the mature MHC complex has been simplified and depicted with a small circle, filled in black.…”

Regulation of MHC Class I by Viruses

“…Another recently identified protein by EBV, BNLF2a, was shown to prevent the binding of peptides and ATP to TAP (Horst et al 2011). Another HIV-1 protein, Nef, blocks the TAP transport of peptides into the ER (Cohen et al 1999;Williams et al 2002b).…”