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Human Cytomegalovirus Immediate Early Glycoprotein US3 Retains MHC Class I Molecules by Transient Association
Author(s) -
Gruhler Albrecht,
Peterson Per A.,
Früh Klaus
Publication year - 2000
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1034/j.1600-0854.2000.010405.x
Subject(s) - biology , glycoprotein , virology , cytomegalovirus , mhc class i , transient (computer programming) , major histocompatibility complex , microbiology and biotechnology , human cytomegalovirus , association (psychology) , immunology , antigen , herpesviridae , virus , viral disease , philosophy , epistemology , computer science , operating system
Human cytomegalovirus (HCMV) interferes with major histocompatibility complex (MHC) class I antigen presentation by a sequential multistep process to escape T cell surveillance. During the immediate early phase of infection, the glycoprotein US3 prevents intracellular transport of MHC class I molecules. Interestingly, US3 displays a significantly shorter half‐life than US3‐retained MHC class I molecules. Here we show that US3 associates only transiently with MHC class I molecules, exits the ER, and is inefficiently retrieved from the Golgi. US3 was degraded in a post‐Golgi compartment, most likely lysosomes, because: i) Brefeldin A treatment prolonged the half‐life of US3; and ii) US3 co‐localized with the lysosomal marker protein LAMP in chloroquine‐treated cells. In contrast, MHC class I molecules remained stable in the ER. Upon inhibition of protein synthesis MHC class I molecules were released suggesting that a continuous supply of newly synthesized US3 molecules is required for inhibition of transport. Thus, US3 does not seem to retain MHC class I molecules by a retrieval mechanism. Instead, our observations are consistent with US3 preventing MHC class I trafficking by blocking forward transport.