This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Keppler, O. T. Articles by Fackler, O. T. Search for Related Content PubMed PubMed Citation Articles by Keppler, O. T. Articles by Fackler, O. T.

 Previous Article  |  Next Article 

Journal of Virology, February 2005, p. 1655-1665, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1655-1665.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Rodent Cells Support Key Functions of the Human Immunodeficiency Virus Type 1 Pathogenicity Factor Nef

Department of Virology, University of Heidelberg, Heidelberg, Germany,¹ Gladstone Institute of Virology and Immunology,² Departments of Medicine and Microbiology and Immunology, University of California, San Francisco, California³

Received 17 May 2004/ Accepted 20 September 2004

After infection with human immunodeficiency virus (HIV), progression toward immunodeficiency is governed by a complex interplay of viral and host determinants. The viral accessory protein Nef is a key factor for the development of AIDS. Strains of HIV and simian immunodeficiency virus that lack functional nef genes either do not induce AIDS or do so only after a significant delay. The validity of a transgenic-small-animal model for de novo infection by HIV will depend on its ability to recapitulate the actions of critical factors of viral pathogenicity, such as Nef. We assessed the ability of rat, mouse, and hamster cells to support key effector functions of Nef. In cell lines from rodents, the subcellular distribution of wild-type HIV type 1 strain SF2 Nef and mutants was comparable to that in human cells. Nef downregulated human CD4 from the cell surface, was associated with p21-activated kinase activity, and enhanced the infectivity of HIV-1 virions. Importantly, these Nef-induced effects, as well as the downregulation of rat CD4 and major histocompatibility complex class I molecules, could also be demonstrated in primary T lymphocytes and macrophages from human CD4-transgenic rats. Thus, HIV-1 Nef exerts key functions in rodent cells. In line with our ongoing efforts to establish a transgenic-rat model of HIV disease, these results indicate that important aspects of viral pathogenesis could be addressed in a transgenic-rodent model permissive for de novo infection and that such a model would be valuable for evaluating the function of Nef in vivo.

This article has been cited by other articles:

• Goffinet, C., Allespach, I., Keppler, O. T. (2007). HIV-susceptible transgenic rats allow rapid preclinical testing of antiviral compounds targeting virus entry or reverse transcription. Proc. Natl. Acad. Sci. USA 104: 1015-1020 [Abstract] [Full Text]  
• Michel, N., Ganter, K., Venzke, S., Bitzegeio, J., Fackler, O. T., Keppler, O. T. (2006). The Nef Protein of Human Immunodeficiency Virus Is a Broad-Spectrum Modulator of Chemokine Receptor Cell Surface Levels That Acts Independently of Classical Motifs for Receptor Endocytosis and G{alpha}i Signaling. Mol. Biol. Cell 17: 3578-3590 [Abstract] [Full Text]  
• Haller, C., Rauch, S., Michel, N., Hannemann, S., Lehmann, M. J., Keppler, O. T., Fackler, O. T. (2006). The HIV-1 Pathogenicity Factor Nef Interferes with Maturation of Stimulatory T-lymphocyte Contacts by Modulation of N-Wasp Activity. J. Biol. Chem. 281: 19618-19630 [Abstract] [Full Text]  
• Vincent, P., Priceputu, E., Kay, D., Saksela, K., Jolicoeur, P., Hanna, Z. (2006). Activation of p21-activated Kinase 2 and Its Association with Nef Are Conserved in Murine Cells but Are Not Sufficient to Induce an AIDS-like Disease in CD4C/HIV Transgenic Mice. J. Biol. Chem. 281: 6940-6954 [Abstract] [Full Text]  
• Keppler, O. T., Tibroni, N., Venzke, S., Rauch, S., Fackler, O. T. (2006). Modulation of specific surface receptors and activation sensitization in primary resting CD4+ T lymphocytes by the Nef protein of HIV-1. J. Leukoc. Biol. 79: 616-627 [Abstract] [Full Text]  
• Fenard, D., Yonemoto, W., de Noronha, C., Cavrois, M., Williams, S. A., Greene, W. C. (2005). Nef Is Physically Recruited into the Immunological Synapse and Potentiates T Cell Activation Early after TCR Engagement. J. Immunol. 175: 6050-6057 [Abstract] [Full Text]