Abstract
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 chloroquinetreated 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.
Original language | English (US) |
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Pages (from-to) | 318-325 |
Number of pages | 8 |
Journal | Traffic |
Volume | 1 |
Issue number | 4 |
DOIs | |
State | Published - 2000 |
Externally published | Yes |
Keywords
- Antigen presentation
- Coatomer
- Endoplasmic reticulum
- Golgi
- Herpesvirus
- Histocompatibility complex
- Immune escape
- Intracellular protein transport
- Lysosome
- Protein degradation
- Retention
- Retrieval
ASJC Scopus subject areas
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology