Nature Medicine
5, 1039 - 1043 (1999)
doi:10.1038/12478
Cytomegalovirus US2 destroys two components of the MHC class II pathway,
preventing recognition by CD4+ T cellsRoman Tomazin1, Jessica Boname1, , Nagendra R. Hegde1, David M. Lewinsohn2, Yoram Altschuler3, Thomas R. Jones4, Peter Cresswell5, Jay A. Nelson1, Stanley R. Riddell6
& David C. Johnson11
Department of Molecular Microbiology & Immunology, Oregon Health Sciences University, Portland, Oregon 97201, USA
2
Division of Pulmonary and Critical Care Medicine, Portland VA Medical Center, Portland, Oregon 97207, USA
3
Department of Anatomy, University of California, San Francisco, California 94143, USA
4
Department of Molecular Biology, Wyeth-Ayerst Research, Pearl River, New York 10965, USA
5
Section of Immunobiology, Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06510, USA
6
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA
7
J.B. present address: Department of Pathology, Cambridge University, Cambridge, UK
Correspondence should be addressed to David C. Johnson johnsoda@ohsu.eduHuman 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 immunity2,
3. Monocyte/macrophages are important
host cells for HCMV, serving as a latent reservoir and as a means of dissemination
throughout the body4. 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- and DM-. 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.
|
