A VIRAL ER-RESIDENT GLYCOPROTEIN INACTIVATES THE MHC-ENCODED PEPTIDE TRANSPORTER

Human cytomegalovirus inhibits peptide import into the endoplasmic ret iculum (ER) by the MHC-encoded TAP peptide transporter. We identified the open reading frame US6 to mediate this effect. Expression of the 2 1 kDa US6 glycoprotein in human cytomegalovirus-infected cells correla tes with the inhibition of peptide transport during infection. The sub cellular localization of US6 is ER restricted and is identical with TA P. US6 protein is found in complexes with TAP1/2, MHC class I heavy ch ain, beta(2)-microglobulin, calnexin, calreticulin, and tapasin. TAP i nhibition, however, is independent of the presence of class I heavy ch ain and tapasin. The results establish a new mechanism for viral immun e escape and a novel role for ER-resident proteins to regulate TAP via its luminal face.