Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 334K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lee, S.-H. Articles by Vidal, S. M. Search for Related Content PubMed PubMed Citation Articles by Lee, S.-H. Articles by Vidal, S. M. Social Bookmarking                      What's this?

Transgenic Expression of the Activating Natural Killer Receptor Ly49H Confers Resistance to Cytomegalovirus in Genetically Susceptible Mice

Seung-Hwan Lee¹, Ahmed Zafer², Yves de Repentigny², Rashmi Kothary², Michel L. Tremblay³, Philippe Gros³, Pascale Duplay⁴, John R. Webb¹ and Silvia M. Vidal¹

¹ Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada
² Centre for Molecular Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario K1H 8L6, Canada
³ Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada
⁴ Institut National de la Recherche Scientifique-Institut Armand-Frappier, Universite du Quebec, Laval, Quebec H7V 1B7, Canada

Address correspondence to Silvia M. Vidal, Faculty of Medicine, University of Ottawa, Room 4207, 451 Smyth Rd., Ottawa, Ontario K1H 8M5, Canada. Phone: 613-562-5800 (8592); Fax: 613-562-5452; E-mail: svidal{at}uottawa.ca

Natural resistance to infection with mouse cytomegalovirus (MCMV) is controlled by a dominant locus, Cmv1. Cmv1 is linked to the Ly49 family of natural killer receptors on distal chromosome 6. While some studies localized Cmv1 as distal to the Ly49 gene cluster, genetic and functional analysis identified Ly49h as a pivotal factor in resistance to MCMV. The role of these two independent genomic domains in MCMV resistance was evaluated by functional complementation using transgenesis of bacterial artificial chromosomes (BAC) in genetically susceptible mice. Phenotypic and genetic characterization of the transgenic animals traced the resistance gene to a single region spanning the Ly49h gene. The appearance of the Ly49H protein in NK cells of transgenic mice coincided with the emergence of MCMV resistance, and there was a threshold Ly49H protein level associated with full recovery. Finally, transgenic expression of Ly49H in the context of either of the two independent susceptibility alleles, Cmv1^sBALB or Cmv1^sFVB, conferred resistance to MCMV infection. These results demonstrate that Ly49h is necessary and sufficient to confer MCMV resistance, and formally demonstrate allelism between Cmv1 and Ly49h. This panel of transgenic animals provides a unique resource to study possible pleiotropic effect of Cmv1.

Key Words: genetic complementation test • natural immunity • animal model • immunogenetics • natural killer cells

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

This article has been cited by other articles:

• Kielczewska, A., Pyzik, M., Sun, T., Krmpotic, A., Lodoen, M. B., Munks, M. W., Babic, M., Hill, A. B., Koszinowski, U. H., Jonjic, S., Lanier, L. L., Vidal, S. M. (2009). Ly49P recognition of cytomegalovirus-infected cells expressing H2-Dk and CMV-encoded m04 correlates with the NK cell antiviral response. JEM 206: 515-523 [Abstract] [Full Text]  
• Fodil-Cornu, N., Lee, S.-H., Belanger, S., Makrigiannis, A. P., Biron, C. A., Buller, R. M., Vidal, S. M. (2008). Ly49h-Deficient C57BL/6 Mice: A New Mouse Cytomegalovirus-Susceptible Model Remains Resistant to Unrelated Pathogens Controlled by the NK Gene Complex. J. Immunol. 181: 6394-6405 [Abstract] [Full Text]  
• Tripathy, S. K., Keyel, P. A., Yang, L., Pingel, J. T., Cheng, T. P., Schneeberger, A., Yokoyama, W. M. (2008). Continuous engagement of a self-specific activation receptor induces NK cell tolerance. JEM 205: 1829-1841 [Abstract] [Full Text]  
• Davis, A. H., Guseva, N. V., Ball, B. L., Heusel, J. W. (2008). Characterization of Murine Cytomegalovirus m157 from Infected Cells and Identification of Critical Residues Mediating Recognition by the NK Cell Receptor Ly49H. J. Immunol. 181: 265-275 [Abstract] [Full Text]  
• Iizuka, K., Nakajima, C., Iizuka, Y.-M., Takase, M., Kato, T., Noda, S., Tanaka, K., Kanagawa, O. (2007). Protection from Lethal Infection by Adoptive Transfer of CD8 T Cells Genetically Engineered to Express Virus-Specific Innate Immune Receptor. J. Immunol. 179: 1122-1128 [Abstract] [Full Text]  
• Adams, E. J., Juo, Z. S., Venook, R. T., Boulanger, M. J., Arase, H., Lanier, L. L., Garcia, K. C. (2007). Structural elucidation of the m157 mouse cytomegalovirus ligand for Ly49 natural killer cell receptors. Proc. Natl. Acad. Sci. USA 104: 10128-10133 [Abstract] [Full Text]  
• Crozat, K., Hoebe, K., Ugolini, S., Hong, N. A., Janssen, E., Rutschmann, S., Mudd, S., Sovath, S., Vivier, E., Beutler, B. (2007). Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis. JEM 204: 853-863 [Abstract] [Full Text]  
• Kielczewska, A., Kim, H.-S., Lanier, L. L., Dimasi, N., Vidal, S. M. (2007). Critical Residues at the Ly49 Natural Killer Receptor's Homodimer Interface Determine Functional Recognition of m157, a Mouse Cytomegalovirus MHC Class I-Like Protein. J. Immunol. 178: 369-377 [Abstract] [Full Text]  
• French, A. R., Sjolin, H., Kim, S., Koka, R., Yang, L., Young, D. A., Cerboni, C., Tomasello, E., Ma, A., Vivier, E., Karre, K., Yokoyama, W. M. (2006). DAP12 Signaling Directly Augments Proproliferative Cytokine Stimulation of NK Cells during Viral Infections. J. Immunol. 177: 4981-4990 [Abstract] [Full Text]  
• Szomolanyi-Tsuda, E., Liang, X., Welsh, R. M., Kurt-Jones, E. A., Finberg, R. W. (2006). Role for TLR2 in NK Cell-Mediated Control of Murine Cytomegalovirus In Vivo. J. Virol. 80: 4286-4291 [Abstract] [Full Text]  
• Adam, S. G., Caraux, A., Fodil-Cornu, N., Loredo-Osti, J. C., Lesjean-Pottier, S., Jaubert, J., Bubic, I., Jonjic, S., Guenet, J.-L., Vidal, S. M., Colucci, F. (2006). Cmv4, a New Locus Linked to the NK Cell Gene Complex, Controls Innate Resistance to Cytomegalovirus in Wild-Derived Mice. J. Immunol. 176: 5478-5485 [Abstract] [Full Text]  
• Walzer, T., Dalod, M., Robbins, S. H., Zitvogel, L., Vivier, E. (2005). Natural-killer cells and dendritic cells: "l'union fait la force". Blood 106: 2252-2258 [Abstract] [Full Text]  
• Fortier, A., Min-Oo, G., Forbes, J., Lam-Yuk-Tseung, S., Gros, P. (2005). Single gene effects in mouse models of host: pathogen interactions. J. Leukoc. Biol. 77: 868-877 [Abstract] [Full Text]  
• Picone, O., Costa, J.-M., Chaix, M.-L., Ville, Y., Rouzioux, C., Leruez-Ville, M. (2005). Human Cytomegalovirus UL144 Gene Polymorphisms in Congenital Infections. J. Clin. Microbiol. 43: 25-29 [Abstract] [Full Text]  
• Loh, J., Chu, D. T., O'Guin, A. K., Yokoyama, W. M., Virgin, H. W. IV (2005). Natural Killer Cells Utilize both Perforin and Gamma Interferon To Regulate Murine Cytomegalovirus Infection in the Spleen and Liver. J. Virol. 79: 661-667 [Abstract] [Full Text]  
• Rodriguez, M., Sabastian, P., Clark, P., Brown, M. G. (2004). Cmv1-Independent Antiviral Role of NK Cells Revealed in Murine Cytomegalovirus-Infected New Zealand White Mice. J. Immunol. 173: 6312-6318 [Abstract] [Full Text]  
• Halford, W. P., Balliet, J. W., Gebhardt, B. M. (2004). Re-Evaluating Natural Resistance to Herpes Simplex Virus Type 1. J. Virol. 78: 10086-10095 [Abstract] [Full Text]  
• Bubic, I., Wagner, M., Krmpotic, A., Saulig, T., Kim, S., Yokoyama, W. M., Jonjic, S., Koszinowski, U. H. (2004). Gain of Virulence Caused by Loss of a Gene in Murine Cytomegalovirus. J. Virol. 78: 7536-7544 [Abstract] [Full Text]  
• Robbins, S. H., Tessmer, M. S., Mikayama, T., Brossay, L. (2004). Expansion and Contraction of the NK Cell Compartment in Response to Murine Cytomegalovirus Infection. J. Immunol. 173: 259-266 [Abstract] [Full Text]  
• Froberg, M. K. (2004). CMV Escapes!. Annals of Clinical & Laboratory Science 34: 123-130 [Abstract] [Full Text]  
• Voigt, V., Forbes, C. A., Tonkin, J. N., Degli-Esposti, M. A., Smith, H. R. C., Yokoyama, W. M., Scalzo, A. A. (2003). Murine cytomegalovirus m157 mutation and variation leads to immune evasion of natural killer cells. Proc. Natl. Acad. Sci. USA 100: 13483-13488 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS