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

Albrecht Gruhler, Per A. Peterson, Klaus Früh

Research output: Contribution to journalArticle

38 Scopus citations

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
DOIs
StatePublished - Jan 1 2000

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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

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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