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 Lewinsohn, Yoram Altschuler, Thomas R. Jones, Peter Cresswell, Jay Nelson, Stanley R. Riddell, David Johnson

Research output: Contribution to journalArticle

195 Citations (Scopus)

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 1999

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T-cells
Cytomegalovirus
Macrophages
T-Lymphocytes
CD4 Antigens
Proteins
Transplantation (surgical)
Antigens
Degradation
Histocompatibility Antigens Class II
Endothelial cells
HLA-DR Antigens
Immune Evasion
Tissue Transplantation
Viruses
Herpesviridae
Antigen Presentation
Bone
Bone Marrow Transplantation
Neuroglia

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Cytomegalovirus US2 destroys two components of the MHC class II pathway, preventing recognition by CD4+ T cells. / Tomazin, Roman; Boname, Jessica; Hedge, Nagendra R.; Lewinsohn, David; Altschuler, Yoram; Jones, Thomas R.; Cresswell, Peter; Nelson, Jay; Riddell, Stanley R.; Johnson, David.

In: Nature Medicine, Vol. 5, No. 9, 09.1999, p. 1039-1043.

Research output: Contribution to journalArticle

Tomazin, Roman ; Boname, Jessica ; Hedge, Nagendra R. ; Lewinsohn, David ; Altschuler, Yoram ; Jones, Thomas R. ; Cresswell, Peter ; Nelson, Jay ; Riddell, Stanley R. ; Johnson, David. / Cytomegalovirus US2 destroys two components of the MHC class II pathway, preventing recognition by CD4+ T cells. In: Nature Medicine. 1999 ; Vol. 5, No. 9. pp. 1039-1043.
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