J. Exp. Med., Volume 188, Number 3, August 3, 1998 497-503

Trophoblast Class I Major Histocompatibility Complex (MHC) Products Are Resistant to Rapid Degradation Imposed by the Human Cytomegalovirus (HCMV) Gene Products US2 and US11

By Danny J. Schust,^* Domenico Tortorella,^* Jörg Seebach, Cindy Phan,^* and Hidde L. Ploegh^*

From the ^* Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115; and the  Transplantation Biology Research Center, Massachusetts General Hospital, Boston, Massachusetts 02119

US11 and US2 encode gene products expressed early in the replicative cycle of human cytomegalovirus (HCMV), which cause dislocation of human and murine major histocompatibility complex (MHC) class I molecules from the lumen of the endoplasmic reticulum to the cytosol, where the class I heavy chains are rapidly degraded. Human histocompatibility leukocyte antigens (HLA)-C and HLA-G are uniquely resistant to the effects of both US11 and US2 in a human trophoblast cell line as well as in porcine endothelial cells stably transfected with human class I genes. Dislocation and degradation of MHC class I heavy chains do not appear to involve cell type-specific factors, as US11 and US2 are fully active in this xenogeneic model. Importantly, trophoblasts HLA-G and HLA-C possess unique characteristics that allow their escape from HCMV-associated MHC class I degradation. Trophoblast class I molecules could serve not only to block recognition by natural killer cells, but also to guide virus-specific HLA-C- and possibly HLA-G-restricted cytotoxic T-lymphocytes to their targets.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Thilo, C., Berglund, P., Applequist, S. E., Yewdell, J. W., Ljunggren, H.-G., Achour, A. (2006). Dissection of the Interaction of the Human Cytomegalovirus-derived US2 Protein with Major Histocompatibility Complex Class I Molecules: PROMINENT ROLE OF A SINGLE ARGININE RESIDUE IN HUMAN LEUKOCYTE ANTIGEN-A2. J. Biol. Chem. 281: 8950-8957 [Abstract] [Full Text]  
• Mavoungou, E. (2006). Interactions between natural killer cells, cortisol and prolactin in malaria during pregnancy.. Clin Med Res 4: 33-41 [Abstract] [Full Text]  
• Iannello, A., Debbeche, O., Martin, E., Attalah, L. H., Samarani, S., Ahmad, A. (2006). Viral strategies for evading antiviral cellular immune responses of the host. J. Leukoc. Biol. 79: 16-35 [Abstract] [Full Text]  
• Gazit, R., Garty, B.-Z., Monselise, Y., Hoffer, V., Finkelstein, Y., Markel, G., Katz, G., Hanna, J., Achdout, H., Gruda, R., Gonen-Gross, T., Mandelboim, O. (2004). Expression of KIR2DL1 on the entire NK cell population: a possible novel immunodeficiency syndrome. Blood 103: 1965-1966 [Full Text]  
• Barel, M. T., Ressing, M., Pizzato, N., van Leeuwen, D., Le Bouteiller, P., Lenfant, F., Wiertz, E. J. H. J. (2003). Human Cytomegalovirus-Encoded US2 Differentially Affects Surface Expression of MHC Class I Locus Products and Targets Membrane-Bound, but Not Soluble HLA-G1 for Degradation. J. Immunol. 171: 6757-6765 [Abstract] [Full Text]  
• Terauchi, M., Koi, H., Hayano, C., Toyama-Sorimachi, N., Karasuyama, H., Yamanashi, Y., Aso, T., Shirakata, M. (2003). Placental Extravillous Cytotrophoblasts Persistently Express Class I Major Histocompatibility Complex Molecules after Human Cytomegalovirus Infection. J. Virol. 77: 8187-8195 [Abstract] [Full Text]  
• Arieh, S. V.-B., Laham, N., Schechter, C., Yewdell, J. W., Coligan, J. E., Ehrlich, R. (2003). A single viral protein HCMV US2 affects antigen presentation and intracellular iron homeostasis by degradation of classical HLA class I and HFE molecules. Blood 101: 2858-2864 [Abstract] [Full Text]  
• Furman, M. H., Dey, N., Tortorella, D., Ploegh, H. L. (2002). The Human Cytomegalovirus US10 Gene Product Delays Trafficking of Major Histocompatibility Complex Class I Molecules. J. Virol. 76: 11753-11756 [Abstract] [Full Text]  
• Cebulla, C. M., Miller, D. M., Zhang, Y., Rahill, B. M., Zimmerman, P., Robinson, J. M., Sedmak, D. D. (2002). Human Cytomegalovirus Disrupts Constitutive MHC Class II Expression. J. Immunol. 169: 167-176 [Abstract] [Full Text]  
• Basta, S., Chen, W., Bennink, J. R., Yewdell, J. W. (2002). Inhibitory Effects of Cytomegalovirus Proteins US2 and US11 Point to Contributions from Direct Priming and Cross-Priming in Induction of Vaccinia Virus-Specific CD8+ T Cells. J. Immunol. 168: 5403-5408 [Abstract] [Full Text]  
• Rehm, A., Engelsberg, A., Tortorella, D., Korner, I. J., Lehmann, I., Ploegh, H. L., Hopken, U. E. (2002). Human Cytomegalovirus Gene Products US2 and US11 Differ in Their Ability To Attack Major Histocompatibility Class I Heavy Chains in Dendritic Cells. J. Virol. 76: 5043-5050 [Abstract] [Full Text]  
• Park, B., Oh, H., Lee, S., Song, Y., Shin, J., Sung, Y. C., Hwang, S.-Y., Ahn, K. (2002). The MHC Class I Homolog of Human Cytomegalovirus Is Resistant to Down-Regulation Mediated by the Unique Short Region Protein (US)2, US3, US6, and US11 Gene Products. J. Immunol. 168: 3464-3469 [Abstract] [Full Text]  
• Ben-Arieh, S. V., Zimerman, B., Smorodinsky, N. I., Yaacubovicz, M., Schechter, C., Bacik, I., Gibbs, J., Bennink, J. R., Yewdell, J. W., Coligan, J. E., Firat, H., Lemonnier, F., Ehrlich, R. (2001). Human Cytomegalovirus Protein US2 Interferes with the Expression of Human HFE, a Nonclassical Class I Major Histocompatibility Complex Molecule That Regulates Iron Homeostasis. J. Virol. 75: 10557-10562 [Abstract] [Full Text]  
• Johnson, J. M., Nicot, C., Fullen, J., Ciminale, V., Casareto, L., Mulloy, J. C., Jacobson, S., Franchini, G. (2001). Free Major Histocompatibility Complex Class I Heavy Chain Is Preferentially Targeted for Degradation by Human T-Cell Leukemia/Lymphotropic Virus Type 1 p12I Protein. J. Virol. 75: 6086-6094 [Abstract] [Full Text]  
• Gewurz, B. E., Gaudet, R., Tortorella, D., Wang, E. W., Ploegh, H. L., Wiley, D. C. (2001). From the Cover: Antigen presentation subverted: Structure of the human cytomegalovirus protein US2 bound to the class I molecule HLA-A2. Proc. Natl. Acad. Sci. USA 98: 6794-6799 [Abstract] [Full Text]  
• Gewurz, B. E., Wang, E. W., Tortorella, D., Schust, D. J., Ploegh, H. L. (2001). Human Cytomegalovirus US2 Endoplasmic Reticulum-Lumenal Domain Dictates Association with Major Histocompatibility Complex Class I in a Locus-Specific Manner. J. Virol. 75: 5197-5204 [Abstract] [Full Text]  
• Fisher, S., Genbacev, O., Maidji, E., Pereira, L. (2000). Human Cytomegalovirus Infection of Placental Cytotrophoblasts In Vitro and In Utero: Implications for Transmission and Pathogenesis. J. Virol. 74: 6808-6820 [Abstract] [Full Text]  
• Onno, M., Pangault, C., Le Friec, G., Guilloux, V., Andre, P., Fauchet, R. (2000). Modulation of HLA-G Antigens Expression by Human Cytomegalovirus: Specific Induction in Activated Macrophages Harboring Human Cytomegalovirus Infection. J. Immunol. 164: 6426-6434 [Abstract] [Full Text]  
• Berger, C., Xuereb, S., Johnson, D. C., Watanabe, K. S., Kiem, H.-P., Greenberg, P. D., Riddell, S. R. (2000). Expression of Herpes Simplex Virus ICP47 and Human Cytomegalovirus US11 Prevents Recognition of Transgene Products by CD8+ Cytotoxic T Lymphocytes. J. Virol. 74: 4465-4473 [Abstract] [Full Text]  
• Ulbrecht, M., Martinozzi, S., Grzeschik, M., Hengel, H., Ellwart, J. W., Pla, M., Weiss, E. H. (2000). Cutting Edge: The Human Cytomegalovirus UL40 Gene Product Contains a Ligand for HLA-E and Prevents NK Cell-Mediated Lysis. J. Immunol. 164: 5019-5022 [Abstract] [Full Text]  
• Jun, Y., Kim, E., Jin, M., Sung, H. C., Han, H., Geraghty, D. E., Ahn, K. (2000). Human Cytomegalovirus Gene Products US3 and US6 Down-Regulate Trophoblast Class I MHC Molecules. J. Immunol. 164: 805-811 [Abstract] [Full Text]  
• Goldman-Wohl, D.S., Ariel, I., Greenfield, C., Hochner-Celnikier, D., Cross, J., Fisher, S., Yagel, S. (2000). Lack of human leukocyte antigen-G expression in extravillous trophoblasts is associated with pre-eclampsia. Mol Hum Reprod 6: 88-95 [Abstract] [Full Text]  
• Zhong, G., Fan, T., Liu, L. (1999). Chlamydia Inhibits Interferon gamma -inducible Major Histocompatibility Complex Class II Expression by Degradation of  Upstream Stimulatory Factor 1 . JEM 189: 1931-1938 [Abstract] [Full Text]  
• Lefebvre, S., Berrih-Aknin, S., Adrian, F., Moreau, P., Poea, S., Gourand, L., Dausset, J., Carosella, E. D., Paul, P. (2001). A Specific Interferon (IFN)-stimulated Response Element of the Distal HLA-G Promoter Binds IFN-regulatory Factor 1 and Mediates Enhancement of This Nonclassical Class I Gene by IFN-beta. J. Biol. Chem. 276: 6133-6139 [Abstract] [Full Text]  
• Furman, M. H., Ploegh, H. L., Tortorella, D. (2002). Membrane-specific, Host-derived Factors Are Required for US2- and US11-mediated Degradation of Major Histocompatibility Complex Class I Molecules. J. Biol. Chem. 277: 3258-3267 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS