CYTOMEGALOVIRUS SELECTIVELY BLOCKS ANTIGEN-PROCESSING AND PRESENTATION OF ITS IMMEDIATE-EARLY GENE-PRODUCT

RECOGNITION of virus-infected cells by CD8(+) cytotoxic T lymphocytes requires that the viral proteins be processed into peptides, the deriv ed peptides transported into the endoplasmic reticulum and inserted in to the binding groove of a major histocompatability complex class I mo lecule, and the antigenic complex exported to the cell surface(1). How ever, viral pathogens can disrupt this process and interfere with immu ne recognition(1-4). These mechanisms may be vital to large viruses su ch as human cytomegalovirus (CMV), which causes persistent infection d espite producing over 200 potentially antigenic proteins during the se quential immediate-early, early and late phases of viral gene expressi on(5,6). Products of CMV early-phase gene expression can globally bloc k class I presentation(7-10) and prevent recognition of infected cells by cytotoxic T lymphocytes, but an essential viral transcription fact or, the 72K principal immediate-early protein, is abundantly expressed before this blockade. However, only a few host CD8(+) cytotoxic T lym phocytes specific for immediate-early protein are present in seroposit ive individuals, and these lyse CMV-infected cells poorly(11). Here we demonstrate selective abrogation of immediate-early peptide presentat ion by a CMV matrix protein with associated kinase activity and sugges t that modification of a viral protein can result in limiting access t o the processing machinery and evasion of cytotoxic-T-cell recognition .