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) |
|---|---|
| Pages (from-to) | 318-325 |
| Number of pages | 8 |
| Journal | Traffic |
| Volume | 1 |
| Issue number | 4 |
| State | Published - 2000 |
| Externally published | Yes |
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Keywords
- Antigen presentation
- Coatomer
- Endoplasmic reticulum
- Golgi
- Herpesvirus
- Histocompatibility complex
- Immune escape
- Intracellular protein transport
- Lysosome
- Protein degradation
- Retention
- Retrieval
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Genetics
- Molecular Biology
- Structural Biology
Cite this
Human cytomegalovirus immediate early glycoprotein US3 retains MHC class I molecules by transient association. / Gruhler, Albrecht; Peterson, Per A.; Frueh, Klaus.
In: Traffic, Vol. 1, No. 4, 2000, p. 318-325.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Human cytomegalovirus immediate early glycoprotein US3 retains MHC class I molecules by transient association
AU - Gruhler, Albrecht
AU - Peterson, Per A.
AU - Frueh, Klaus
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Antigen presentation
KW - Coatomer
KW - Endoplasmic reticulum
KW - Golgi
KW - Herpesvirus
KW - Histocompatibility complex
KW - Immune escape
KW - Intracellular protein transport
KW - Lysosome
KW - Protein degradation
KW - Retention
KW - Retrieval
UR - http://www.scopus.com/inward/record.url?scp=0034172843&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034172843&partnerID=8YFLogxK
M3 - Article
VL - 1
SP - 318
EP - 325
JO - Traffic
JF - Traffic
SN - 1398-9219
IS - 4
ER -