Structure function relationship in human cytomegalovirus immune evasion

Abstract

The pathogen, human cytomegalovirus (HCMV) is a herpes virus that causes severe morbidity and mortality in immunologically weak individuals. The virus employs multifaceted strategies to evade the host immune system thereby enabling it to establish persistent infection. One of the immune evasion strategies used by HCMV is the modulation of the pathways of antigen newlinepresentation. A wealth of information is available about how the virus subverts newlinepresentation by major histocompatibility complex (MHC) Class I but very few details of Class II evasion have been reported. The HCMV protein US2 has been shown to interfere with the Class II presentation by using the cellular mechanism of endoplasmic reticulum-associated degradation (ERAD) to degrade the Class II proteins DRand#945; and DMand#945;. However, the specifics of how Class II proteins are targeted by US2 are not well understood. The aim of the current study was to identify the domains of MHC Class II DRand#945; protein required for interaction with HCMV immune evasion protein US2 and also newlineunderstand the differential effect of US2 in handling the MHC Class I and Class II DRand#945; proteins. Experiments using a panel of domain deletion mutants of Class II DRand#945; suggested that the cytosolic tail of DRand#945; played a role in its interaction with US2.