Human cytomegalovirus: Host immune modulation by the viral US3 gene

Human cytomegalovirus (HCMV) is a common infection, opportunistically causing disease in people with immune system deficits. HCMV expresses several proteins that contribute to avoidance of the host immune response. The US3 gene is one of the first immune evasion genes expressed following infection. Expression of the US3 gene is highly regulated, with the gene encoding autoregulatory proteins. The largest of the US3 proteins, a 22 kDa resident endoplasmic reticulum protein, binds to MHC class I heavy chain complexes and components of the peptide loading complex, delaying the maturation of the MHC class I complexes and presentation of viral antigen on the surface of infected cells. A smaller US3 protein, a 17 kDa US3 protein, competes with the 22 kDa for protein interactions, counteracting, in part, the effects of the larger protein. The US3 amino acid sequence is highly conserved among clinical isolates and laboratory strains, suggesting an important role for this gene in natural infections in the human host.