FUNCTIONAL ROLES OF IMMEDIATE-EARLY PROTEINS ENCODED BY THE HUMAN CYTOMEGALOVIRUS UL36-38, UL115-119, TRS1 IRS1 AND US3 LOCI/

Human cytomegalovirus (HCMV) encodes multiple regulatory proteins at i mmediate early (IE) times of infection. Ancillary IE proteins are enco ded by the UL36-38, UL115-119, TRS1/IRS1 and US3 loci. In contrast to the major IE nuclear proteins, several of the ancillary IE proteins ar e type I integral membrane N-glycoproteins. Nonetheless, all of the an cillary proteins examined to date have the ability to regulate nuclear gene expression and to interact cooperatively. Significantly, product s from the UL36-38 and TRS1/IRS1 IE loci as well as products from the MIE locus are required for HCMV ori-Lyt DNA replication. Moreover, the products of the UL36 and UL37 IE genes are essential for HCMV growth in human cells. Finally, one ancillary IE glycoprotein, gpUS3, is know n to have a nonregulatory function; that is, gpUS3 binds and retains m ajor histocompatibility complex class I heavy chains in the endoplasmi c reticulum, thereby inhibiting antigen presentation. Thus, the functi onal presence of multiple IE proteins is required during HCMV replicat ion both in vitro and in vivo to orchestrate necessary events for HCMV replication as well as for the survival of the infected host cell.