Human cytomegalovirus immediate early glycoprotein US3 retains MHC class I molecules by transient association

Albrecht Gruhler, Per A. Peterson, Klaus Frueh

Research output: Contribution to journalArticle

38 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)318-325
Number of pages8
JournalTraffic
Volume1
Issue number4
StatePublished - 2000
Externally publishedYes

Fingerprint

Major Histocompatibility Complex
Cytomegalovirus
Glycoproteins
Association reactions
Molecules
Half-Life
Lysosome-Associated Membrane Glycoproteins
Brefeldin A
Histocompatibility Antigens Class I
T-cells
Antigen Presentation
Lysosomes
T-Lymphocytes
Infection
Proteins

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 journalArticle

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