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

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

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

Nat Med. 1999 Sep;5(9):1039-43. Unique Identifier : AIDSLINE MED/99401084
Tomazin R; Boname J; Hegde NR; Lewinsohn DM; Altschuler Y; Jones TR; Cresswell P; Nelson JA; Riddell SR; Johnson DC; Department of Molecular Microbiology & Immunology, Oregon Health; Sciences University, Portland, Oregon 97201, USA.

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-alpha and DM-alpha. 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.

Keywords: JOURNAL ARTICLE Adenoviridae/GENETICS Antigen Presentation/*IMMUNOLOGY Cytomegalovirus/GENETICS/*PHYSIOLOGY CD4-Positive T-Lymphocytes/*IMMUNOLOGY Genetic Vectors Glioblastoma Histocompatibility Antigens Class II/*IMMUNOLOGY/METABOLISM Human HLA-D Antigens/IMMUNOLOGY/METABOLISM HLA-DR Antigens/IMMUNOLOGY/METABOLISM Macrophages/IMMUNOLOGY/METABOLISM/VIROLOGY Precipitin Tests Subcellular Fractions Support, U.S. Gov't, P.H.S. Tumor Cells, Cultured Viral Envelope Proteins/GENETICS/*METABOLISM Virus Latency $KWDimmunology/metabolismhumanhla-dantigens/immunology/metabolismhla-drantigens/immunology/metabolismmacrophages/immunology/metabolism/virologyprecipitintestssubcellularfractionssupport,u$
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