Cutting edge: Adenovirus E19 has two mechanisms for affecting class I MHC expression

Viral strategies for immune evasion include inhibition of various steps in the class I MHC assembly pathway. Here,,ve demonstrate that adenovirus prod uces one gene product with a dual function in this regard. It is well estab lished that adenovirus E19 binds class I molecules and retains them in the endoplasmic reticulum (ER), However, E19 also delays the expression of clas s I alleles to which it cannot tightly bind. Here, we show that E19 binds T AP and acts as a tapasin inhibitor, preventing class I/TAP association. Del ta E19, an E19 mutant lacking the ER retention signal, delays maturation of class I molecules, indicating that E19's inhibition of class I/TAP interac tion is sufficient to delay class I expression. These data identify tapasin inhibition as a novel mechanism of viral immune evasion and suggest that, through this secondary mechanism, adenovirus can affect Ag presentation by MHC alleles that it can only weakly affect by direct retention.