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

 Previous Article  |  Next Article 

Journal of Virology, September 2001, p. 8063-8073, Vol. 75, No. 17
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.17.8063-8073.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Susceptibility of Rat-Derived Cells to Replication by Human Immunodeficiency Virus Type 1

Oliver T. Keppler,1 Wesley Yonemoto,1 Frank J. Welte,1 Kathryn S. Patton,1,dagger Demetris Iacovides,2 Robert E. Atchison,1,Dagger Tuan Ngo,1 David L. Hirschberg,3,§ Roberto F. Speck,1,|| and Mark A. Goldsmith1,4,*

Gladstone Institute of Virology and Immunology1 and Departments of Physiology2 and Medicine,4 School of Medicine, University of California San Francisco, San Francisco, California 94141-9100, and Department of Neurology and Neurological Sciences, Stanford University, Stanford, California 943053

Received 5 April 2001/Accepted 2 June 2001

Progress in developing a small animal model of human immunodeficiency virus type 1 (HIV-1) disease would greatly facilitate studies of transmission, pathogenesis, host immune responses, and antiviral strategies. In this study, we have explored the potential of rats as a susceptible host. In a single replication cycle, rat cell lines Rat2 and Nb2 produced infectious virus at levels 10- to 60-fold lower than those produced by human cells. Rat-derived cells supported substantial levels of early HIV-1 gene expression, which was further enhanced by overexpression of human cyclin T1. Rat cells displayed quantitative, qualitative, and cell-type-specific limitations in the late phase of the HIV-1 replication cycle including relative expression levels of HIV-1 Gag proteins, intracellular Gag processing, and viral egress. Nb2 cells were rendered permissive to HIV-1 R5 viruses by coexpression of human CD4 and CCR5, indicating that the major restriction on HIV-1 replication was at the level of cellular entry. We also found that primary rat lymphocytes, macrophages, and microglia expressed considerable levels of early HIV-1 gene products following infection with pseudotyped HIV-1. Importantly, primary rat macrophages and microglia, but not lymphocytes, also expressed substantial levels of HIV-1 p24 CA and produced infectious virions. Collectively, these results identify the rat as a promising candidate for a transgenic small animal model of HIV-1 infection and highlight pertinent cell-type-specific restrictions that are features of this species.

* Corresponding author. Mailing address: Gladstone Institute of Virology and Immunology, P.O. Box 419100, San Francisco, CA 94141. Phone: (415) 695-3775. Fax: (415) 695-1364. E-mail: mgoldsmith{at}gladstone.ucsf.edu.

dagger Present address: Dynavax Technologies Corporation, Berkeley, CA 94710.

Dagger Present address: Rigel Pharmaceuticals, Inc., South San Francisco, CA 94080.

§ Present address: Agilent Technologies, Palo Alto, CA 94304.

|| Present address: University Hospital Zürich, CH-8091 Zürich, Switzerland.

Journal of Virology, September 2001, p. 8063-8073, Vol. 75, No. 17
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.17.8063-8073.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Geuenich, S., Kaderali, L., Allespach, I., Sertel, S., Keppler, O. T. (2009). Biological Signature Characteristics of Primary Isolates from Human Immunodeficiency Virus Type 1 Group O in Ex Vivo Human Tonsil Histocultures. J. Virol. 83: 10494-10503 [Abstract] [Full Text]  
  • Goffinet, C., Allespach, I., Oberbremer, L., Golden, P. L., Foster, S. A., Johns, B. A., Weatherhead, J. G., Novick, S. J., Chiswell, K. E., Garvey, E. P., Keppler, O. T. (2009). Pharmacovirological Impact of an Integrase Inhibitor on Human Immunodeficiency Virus Type 1 cDNA Species In Vivo. J. Virol. 83: 7706-7717 [Abstract] [Full Text]  
  • Peng, Y., Lin, F.-c., Verardi, P. H., Jones, L. A., Yilma, T. D. (2009). Lower Levels of Gamma Interferon Expressed by a Pseudotyped Single-Cycle Simian Immunodeficiency Virus Enhance Immunogenicity in Rats. J. Virol. 83: 1592-1601 [Abstract] [Full Text]  
  • Sun, J., Zheng, J. H., Zhao, M., Lee, S., Goldstein, H. (2008). Increased In Vivo Activation of Microglia and Astrocytes in the Brains of Mice Transgenic for an Infectious R5 Human Immunodeficiency Virus Type 1 Provirus and for CD4-Specific Expression of Human Cyclin T1 in Response to Stimulation by Lipopolysaccharides. J. Virol. 82: 5562-5572 [Abstract] [Full Text]  
  • 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]  
  • Tsurutani, N., Yasuda, J., Yamamoto, N., Choi, B.-I., Kadoki, M., Iwakura, Y. (2007). Nuclear Import of the Preintegration Complex Is Blocked upon Infection by Human Immunodeficiency Virus Type 1 in Mouse Cells. J. Virol. 81: 677-688 [Abstract] [Full Text]  
  • Venzke, S., Michel, N., Allespach, I., Fackler, O. T., Keppler, O. T. (2006). Expression of Nef Downregulates CXCR4, the Major Coreceptor of Human Immunodeficiency Virus, from the Surfaces of Target Cells and Thereby Enhances Resistance to Superinfection. J. Virol. 80: 11141-11152 [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]  
  • 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]  
  • Sun, J., Soos, T., KewalRamani, V. N., Osiecki, K., Zheng, J. H., Falkin, L., Santambrogio, L., Littman, D. R., Goldstein, H. (2006). CD4-Specific Transgenic Expression of Human Cyclin T1 Markedly Increases Human Immunodeficiency Virus Type 1 (HIV-1) Production by CD4+ T Lymphocytes and Myeloid Cells in Mice Transgenic for a Provirus Encoding a Monocyte-Tropic HIV-1 Isolate. J. Virol. 80: 1850-1862 [Abstract] [Full Text]  
  • Potash, M. J., Chao, W., Bentsman, G., Paris, N., Saini, M., Nitkiewicz, J., Belem, P., Sharer, L., Brooks, A. I., Volsky, D. J. (2005). A mouse model for study of systemic HIV-1 infection, antiviral immune responses, and neuroinvasiveness. Proc. Natl. Acad. Sci. USA 102: 3760-3765 [Abstract] [Full Text]  
  • Keppler, O. T., Allespach, I., Schuller, L., Fenard, D., Greene, W. C., Fackler, O. T. (2005). Rodent Cells Support Key Functions of the Human Immunodeficiency Virus Type 1 Pathogenicity Factor Nef. J. Virol. 79: 1655-1665 [Abstract] [Full Text]  
  • Marozsan, A. J., Fraundorf, E., Abraha, A., Baird, H., Moore, D., Troyer, R., Nankja, I., Arts, E. J. (2004). Relationships between Infectious Titer, Capsid Protein Levels, and Reverse Transcriptase Activities of Diverse Human Immunodeficiency Virus Type 1 Isolates. J. Virol. 78: 11130-11141 [Abstract] [Full Text]  
  • Hatziioannou, T., Cowan, S., Bieniasz, P. D. (2004). Capsid-Dependent and -Independent Postentry Restriction of Primate Lentivirus Tropism in Rodent Cells. J. Virol. 78: 1006-1011 [Abstract] [Full Text]  
  • Koito, A., Kameyama, Y., Cheng-Mayer, C., Matsushita, S. (2003). Susceptibility of Mink (Mustera vision)-Derived Cells to Replication by Human Immunodeficiency Virus Type 1. J. Virol. 77: 5109-5117 [Abstract] [Full Text]  
  • Yedavalli, V. S. R. K., Benkirane, M., Jeang, K.-T. (2003). Tat and Trans-activation-responsive (TAR) RNA-independent Induction of HIV-1 Long Terminal Repeat by Human and Murine Cyclin T1 Requires Sp1. J. Biol. Chem. 278: 6404-6410 [Abstract] [Full Text]  
  • Twu, C., Liu, N. Q., Popik, W., Bukrinsky, M., Sayre, J., Roberts, J., Rania, S., Bramhandam, V., Roos, K. P., MacLellan, W. R., Fiala, M. (2002). Cardiomyocytes undergo apoptosis in human immunodeficiency virus cardiomyopathy through mitochondrion- and death receptor-controlled pathways. Proc. Natl. Acad. Sci. USA 99: 14386-14391 [Abstract] [Full Text]  
  • Keppler, O. T., Welte, F. J., Ngo, T. A., Chin, P. S., Patton, K. S., Tsou, C.-L., Abbey, N. W., Sharkey, M. E., Grant, R. M., You, Y., Scarborough, J. D., Ellmeier, W., Littman, D. R., Stevenson, M., Charo, I. F., Herndier, B. G., Speck, R. F., Goldsmith, M. A. (2002). Progress Toward a Human CD4/CCR5 Transgenic Rat Model for De Novo Infection by Human Immunodeficiency Virus Type 1. JEM 195: 719-736 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»