Cytomegalovirus US2 destroys two components of the MHC class II pathway, preventing recognition by CD4+ T cells

Roman Tomazin, Jessica Boname, Nagendra R. Hedge, David M. Lewinsohn, Yoram Altschuler, Thomas R. Jones, Peter Cresswell, Jay A. Nelson, Stanley R. Riddell, David C. Johnson

Research output: Contribution to journalArticle

201 Scopus citations

Abstract

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that causes life-threatening disease in patients who are immunosuppressed for bone marrow or tissue transplantation or who have AIDS (ref. 1). HCMV establishes lifelong latent infections and, after periodic reactivation from latency, uses a panel of immune evasion proteins to survive and replicate in the face of robust, fully primed host immunity. Monocyte/macrophages are important host cells for HCMV, serving as a latent reservoir and as a means of dissemination throughout the body. Macrophages and other HCMV-permissive cells, such as endothelial and glial cells, can express MHC class II proteins and present antigens to CD4+ T lymphocytes. Here, we show that the HCMV protein US2 causes degradation of two essential proteins in the MHC class II antigen presentation pathway: HLA-DR-α and DM-α. This was unexpected, as US2 has been shown to cause degradation of MHC class I (refs. 5,6), which has only limited homology with class II proteins. Expression of US2 in cells reduced or abolished their ability to present antigen to CD4+ T lymphocytes. Thus, US2 may allow HCMV-infected macrophages to remain relatively 'invisible' to CD4+ T cells, a property that would be important after virus reactivation.

Original languageEnglish (US)
Pages (from-to)1039-1043
Number of pages5
JournalNature medicine
Volume5
Issue number9
DOIs
StatePublished - Sep 1 1999

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Cytomegalovirus US2 destroys two components of the MHC class II pathway, preventing recognition by CD4+ T cells'. Together they form a unique fingerprint.

  • Cite this