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Journal of Virology, November 2001, p. 10557-10562, Vol. 75, No. 21
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.21.10557-10562.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Human Cytomegalovirus Protein US2 Interferes with the Expression of Human HFE, a Nonclassical Class I Major Histocompatibility Complex Molecule That Regulates Iron Homeostasis

Sayeh Vahdati Ben-Arieh,1 Baruch Zimerman,1 Nechama I. Smorodinsky,1 Margalit Yaacubovicz,1 Chana Schechter,1 Igor Bacik,2 Jim Gibbs,2 Jack R. Bennink,2 Jon W. Yewdell,2 John E. Coligan,3 Hüseyin Firat,4,dagger François Lemonnier,4 and Rachel Ehrlich1,*

Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel1; Laboratory of Viral Diseases2 and Laboratory of Allergic Diseases,3 National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; and Unité d'Immunité Cellulaire Antivirale, Institut Pasteur, Paris, France4

Received 24 April 2001/Accepted 8 August 2001

HFE is a nonclassical class I major histocompatibility complex (MHC) molecule that is mutated in the autosomal recessive iron overload disease hereditary hemochromatosis. There is evidence linking HFE with reduced iron uptake by the transferrin receptor (TfR). Using a panel of HFE and TfR monoclonal antibodies to examine human HFE (hHFE)-expressing cell lines, we demonstrate the expression of stable and fully glycosylated TfR-free and TfR-associated hHFE/beta 2m complexes. We show that both the stability and assembly of hHFE complexes can be modified by the human cytomegalovirus (HCMV) viral protein US2, known to interfere with the expression of classical class I MHC molecules. HCMV US2, but not US11, targets HFE molecules for degradation by the proteasome. Whether this interference with the regulation of iron metabolism by a viral protein is a means of potentiating viral replication remains to be determined. The reduced expression of classical class I MHC and HFE complexes provides the virus with an efficient tool for altering cellular metabolism and escaping certain immune responses.

* Corresponding author. Mailing address: Dept. of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel. Phone: 972 3 640 9238. Fax: 972 3 642 2046. E-mail: rachele{at}post.tau.ac.il.

dagger Present address: Genethon III, CNRS, URA 1923, 91002 Evry Cédex, France.

Journal of Virology, November 2001, p. 10557-10562, Vol. 75, No. 21
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.21.10557-10562.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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