Human cytomegalovirus protein pp71 disrupts major histocompatibility complex class I cell surface expression.
The human cytomegalovirus tegument protein pp71 is the product of the UL82 gene. Roles for pp71 in stimulating gene transcription, increasing infectivity of viral DNA, and the degradation of retinoblastoma family proteins have been described. Here we report a novel function for pp71 in limiting accumulation of cell surface major histocompatibility complex (MHC) class I complexes. MHC molecules were analyzed in glioblastoma cells exposed to a replication-defective adenovirus expressing UL82 (Adpp71) or after transient transfection of the UL82 gene. Accumulation of cell surface MHC class I levels diminished in a specific and dose-dependent manner after exposure to Adpp71 but not after exposure to an adenovirus expressing beta-galactosidase (Adbeta gal). UL82 expression did not interfere with accumulation of either MHC class I heavy-chain transcript or protein, nor did UL82 expression correlate with markers of apoptosis. Rather, UL82 expression correlated with an increased proportion of MHC class I molecules exhibiting sensitivity to endoglycosidase H treatment. Finally, we show that, in cells infected with recombinant virus strain missing all of the unique short region MHC class I evasion genes, disruption of UL82 expression by short, interfering RNAs led to increased accumulation of cell surface MHC class I complexes. These findings support a novel role for HCMV pp71 in disruption of the MHC class I antigen presentation pathway.
Trgovcich
Joanne
J
Department of Pathology, 4162 Graves Hall, 333 West 10th Avenue, The Ohio State University, Columbus, OH 43210, USA. trgovcich-1@medctr.osu.edu
Cebulla
Colleen
C
Zimmerman
Pete
P
Sedmak
Daniel D
DD
D017951:Antigen Presentation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D015536:Down-Regulation; D006026:Glycoside Hydrolases / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D034622:RNA Interference; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D015395:Histocompatibility Antigens Class I; D014764:Viral Proteins; C051298:cytomegalovirus phosphoprotein 71kDa; D006026:Glycoside Hydrolases