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 immediate early (IE) times of infection. Ancillary IE proteins are encoded 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 are type I integral membrane N-glycoproteins. Nonetheless, all of the ancillary proteins examined to date have the ability to regulate nuclear gene expression and to interact cooperatively. Significantly, products 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 known to have a nonregulatory function; that is, gpUS3 binds and retains major histocompatibility complex class I heavy chains in the endoplasmic reticulum, thereby inhibiting antigen presentation. Thus, the functional presence of multiple IE proteins is required during HCMV replication both in vitro and in vivo to orchestrate necessary events for HCMV replication as well as for the survival of the infected host cell.