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Journal of Virology, September 2003, p. 9287-9294, Vol. 77, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.17.9287-9294.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Human Cytomegalovirus US2 Causes Similar Effects on Both Major Histocompatibility Complex Class I and II Proteins in Epithelial and Glial Cells

Nagendra R. Hegde and David C. Johnson*

Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon 97239-3098

Received 27 March 2003/ Accepted 11 June 2003

The human cytomegalovirus (HCMV) glycoprotein US2 specifically binds to major histocompatibility complex (MHC) class I heavy chain (HC) and class II proteins DR{alpha} and DM{alpha}, triggering their degradation by proteasomes. Effects of US2 on class II proteins were originally characterized in HCMV- or adenovirus vector-infected U373 astroglioma cells. Here, we have extended characterization of US2-mediated degradation of class II DR{alpha} to two other cell lines, including biologically relevant epithelial cells. Comparison of the effects of US2 in cells expressing both class I and II proteins demonstrated only a slight preference for class I HC. Moreover, US2 caused degradation of DR{alpha} and DM{alpha} when these proteins were expressed by transfection without DRß, invariant chain (Ii), or DMß. Therefore, US2 binds to {alpha} chains of DR and DM and triggers endoplasmic reticulum degradation without formation of class II DR {alpha}ß/Ii or DM {alpha}ß complexes. Similar levels of degradation of class II {alpha} were observed in cells expressing vastly different amounts of class II, suggesting that cellular factors, other than class II, were limiting. We concluded that US2 has broad effects in a variety of cells that express both class I and II proteins and is relevant to HCMV infection in vivo.

* Corresponding author. Mailing address: Mail Code L-220, Basic Science Rm. 6365, Department of Molecular Microbiology & Immunology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239-3098. Phone: (503) 494-0834. Fax: (503) 494-6862. E-mail: johnsoda{at}ohsu.edu.

Journal of Virology, September 2003, p. 9287-9294, Vol. 77, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.17.9287-9294.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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