Functional analysis of the human cytomegalovirus immune evasion protein, pUS3(22kDa).
Human cytomegalovirus (HCMV) is an important opportunistic pathogen that infrequently causes disease in individuals with mature immune systems. The HCMV US3 gene encodes a 22-kDa protein that interferes with immune recognition of virally infected cells. The 22-kDa US3 protein binds to major histocompatibility complex (MHC) class I complexes, retaining them in the endoplasmic reticulum (ER), thereby decreasing the presentation of viral antigen to cytotoxic T cells. Our studies demonstrate that correct folding of the ER lumenal domain of the US3 protein is essential, but insufficient for interactions with MHC class I complexes. We demonstrate a requirement for the transmembrane domain of the 22-kDa US3 protein, confirming the results of others, and also show that the cytosolic carboxyl-terminal tail influences the function of the protein. Anchoring of the ER-lumenal immunoglobulin-like fold of the US3 protein to the membrane of the endoplasmic reticulum is critical for the binding and retention of MHC class I complexes.
Zhao
Yiqiang
Y
Graduate Program in Biological Sciences, Department of Biomedical Sciences, Ohio University College of Osteopathic Medicine, Athens, OH 45701, USA.
Biegalke
Bonita J
BJ
D001665:Binding Sites; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D008565:Membrane Proteins; D017510:Protein Folding; D013329:Structure-Activity Relationship
D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; C095111:US3 protein, cytomegalovirus