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 Bieniasz, P. D.
Right arrow Articles by Cullen, B. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bieniasz, P. D.
Right arrow Articles by Cullen, B. R.

 Previous Article  |  Next Article 

Journal of Virology, November 2000, p. 9868-9877, Vol. 74, No. 21
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Multiple Blocks to Human Immunodeficiency Virus Type 1 Replication in Rodent Cells

Paul D. Bieniasz1,* and Bryan R. Cullen2

Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016,1 and Howard Hughes Medical Institute and Department of Genetics, Duke University Medical Center, Durham, North Carolina 277102

Received 12 June 2000/Accepted 6 August 2000

The recent identification of human gene products that are required for early steps in the human immunodeficiency virus type 1 (HIV-1) life cycle has raised the possibility that rodents might be engineered to support HIV-1 infection. Therefore, we have examined the ability of modified mouse, rat, and hamster cell lines to support productive HIV-1 replication. Rodent cells, engineered to support Tat function by stable expression of a permissive cyclin T1 protein, proved to be able to support reverse transcription, integration, and early gene expression at levels comparable to those observed in human cell lines. Surprisingly, however, levels of CD4- and coreceptor-dependent virus entry were reduced to a variable but significant extent in both mouse and rat fibroblast cell lines. Additional posttranscriptional defects were observed, including a reduced level of unspliced HIV-1 genomic RNA and reduced structural gene expression. Furthermore, the HIV-1 Gag precursor is generally inefficiently processed and is poorly secreted from mouse and rat cells in a largely noninfectious form. These posttranscriptional defects, together, resulted in a dramatically reduced yield of infectious virus (up to 10,000-fold) over a single cycle of HIV-1 replication, as compared to human cells. Interestingly, these defects were less pronounced in one hamster cell line, CHO, which not only was able to produce infectious HIV-1 particles at a level close to that observed in human cells, but also could support transient, low-level HIV-1 replication. Importantly, the blocks to infectious virus production in mouse and rat cells are recessive, since they can be substantially suppressed by fusion with uninfected human cells. These studies imply the existence of one or more human gene products, either lacking or nonfunctional in most rodent cells that are critical for infectious HIV-1 virion morphogenesis.

* Corresponding author. Mailing address: Aaron Diamond AIDS Research Center, 455 First Ave., New York, NY 10016. Phone: (212) 448-5070. Fax: (212) 448-5159. E-mail: pbienias{at}adarc.adarc.org.

Journal of Virology, November 2000, p. 9868-9877, Vol. 74, No. 21
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Zhang, B., Montelaro, R. C. (2009). Replication of Equine Infectious Anemia Virus in Engineered Mouse NIH 3T3 Cells. J. Virol. 83: 2034-2037 [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]  
  • Wei, M., Yang, Y., Niu, M., Desfosse, L., Kennedy, R., Musier-Forsyth, K., Kleiman, L. (2008). Inability of Human Immunodeficiency Virus Type 1 Produced in Murine Cells To Selectively Incorporate Primer Formula. J. Virol. 82: 12049-12059 [Abstract] [Full Text]  
  • Berro, R., Pedati, C., Kehn-Hall, K., Wu, W., Klase, Z., Even, Y., Geneviere, A.-M., Ammosova, T., Nekhai, S., Kashanchi, F. (2008). CDK13, a New Potential Human Immunodeficiency Virus Type 1 Inhibitory Factor Regulating Viral mRNA Splicing. J. Virol. 82: 7155-7166 [Abstract] [Full Text]  
  • Jin, J., Sturgeon, T., Chen, C., Watkins, S. C., Weisz, O. A., Montelaro, R. C. (2007). Distinct Intracellular Trafficking of Equine Infectious Anemia Virus and Human Immunodeficiency Virus Type 1 Gag during Viral Assembly and Budding Revealed by Bimolecular Fluorescence Complementation Assays. J. Virol. 81: 11226-11235 [Abstract] [Full Text]  
  • Munk, C., Zielonka, J., Constabel, H., Kloke, B.-P., Rengstl, B., Battenberg, M., Bonci, F., Pistello, M., Lochelt, M., Cichutek, K. (2007). Multiple Restrictions of Human Immunodeficiency Virus Type 1 in Feline Cells. J. Virol. 81: 7048-7060 [Abstract] [Full Text]  
  • Sun, Z., Denton, P. W., Estes, J. D., Othieno, F. A., Wei, B. L., Wege, A. K., Melkus, M. W., Padgett-Thomas, A., Zupancic, M., Haase, A. T., Garcia, J. V. (2007). Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1. JEM 204: 705-714 [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]  
  • Berro, R., Kehn, K., de la Fuente, C., Pumfery, A., Adair, R., Wade, J., Colberg-Poley, A. M., Hiscott, J., Kashanchi, F. (2006). Acetylated Tat Regulates Human Immunodeficiency Virus Type 1 Splicing through Its Interaction with the Splicing Regulator p32.. J. Virol. 80: 3189-3204 [Abstract] [Full Text]  
  • Coskun, A. K., van Maanen, M., Nguyen, V., Sutton, R. E. (2006). Human chromosome 2 carries a gene required for production of infectious human immunodeficiency virus type 1.. J. Virol. 80: 3406-3415 [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]  
  • Hatziioannou, T., Martin-Serrano, J., Zang, T., Bieniasz, P. D. (2005). Matrix-Induced Inhibition of Membrane Binding Contributes to Human Immunodeficiency Virus Type 1 Particle Assembly Defects in Murine Cells. J. Virol. 79: 15586-15589 [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]  
  • Wong, S. B. J., Siliciano, R. F. (2005). Contribution of Virus-Like Particles to the Immunogenicity of Human Immunodeficiency Virus Type 1 Gag-Derived Vaccines in Mice. J. Virol. 79: 1701-1712 [Abstract] [Full Text]  
  • Baumann, J. G., Unutmaz, D., Miller, M. D., Breun, S. K. J., Grill, S. M., Mirro, J., Littman, D. R., Rein, A., KewalRamani, V. N. (2004). Murine T Cells Potently Restrict Human Immunodeficiency Virus Infection. J. Virol. 78: 12537-12547 [Abstract] [Full Text]  
  • Berthoux, L., Sebastian, S., Sokolskaja, E., Luban, J. (2004). Lv1 Inhibition of Human Immunodeficiency Virus Type 1 Is Counteracted by Factors That Stimulate Synthesis or Nuclear Translocation of Viral cDNA. J. Virol. 78: 11739-11750 [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]  
  • Shoya, Y., Tokunaga, K., Sawa, H., Maeda, M., Ueno, T., Yoshikawa, T., Hasegawa, H., Sata, T., Kurata, T., Hall, W. W., Cullen, B. R., Takahashi, H. (2003). Human topoisomerase I promotes HIV-1 proviral DNA synthesis: Implications for the species specificity and cellular tropism of HIV-1 infection. Proc. Natl. Acad. Sci. USA 100: 8442-8447 [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]  
  • Marques, S. M. P., Veyrune, J.-L., Shukla, R. R., Kumar, A. (2003). Restriction of Human Immunodeficiency Virus Type 1 Rev Function in Murine A9 Cells Involves the Rev C-Terminal Domain. J. Virol. 77: 3084-3090 [Abstract] [Full Text]  
  • Berthoux, L., Towers, G. J., Gurer, C., Salomoni, P., Pandolfi, P. P., Luban, J. (2003). As2O3 Enhances Retroviral Reverse Transcription and Counteracts Ref1 Antiviral Activity. J. Virol. 77: 3167-3180 [Abstract] [Full Text]  
  • Brunelle, M.-N., Brakier-Gingras, L., Lemay, G. (2003). Replacement of Murine Leukemia Virus Readthrough Mechanism by Human Immunodeficiency Virus Frameshift Allows Synthesis of Viral Proteins and Virus Replication. J. Virol. 77: 3345-3350 [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]  
  • Munk, C., Brandt, S. M., Lucero, G., Landau, N. R. (2002). A dominant block to HIV-1 replication at reverse transcription in simian cells. Proc. Natl. Acad. Sci. USA 99: 13843-13848 [Abstract] [Full Text]  
  • Cowan, S., Hatziioannou, T., Cunningham, T., Muesing, M. A., Gottlinger, H. G., Bieniasz, P. D. (2002). From the Cover: Cellular inhibitors with Fv1-like activity restrict human and simian immunodeficiency virus tropism. Proc. Natl. Acad. Sci. USA 99: 11914-11919 [Abstract] [Full Text]  
  • Lavillette, D., Marin, M., Ruggieri, A., Mallet, F., Cosset, F.-L., Kabat, D. (2002). The Envelope Glycoprotein of Human Endogenous Retrovirus Type W Uses a Divergent Family of Amino Acid Transporters/Cell Surface Receptors. J. Virol. 76: 6442-6452 [Abstract] [Full Text]  
  • Serhan, F., Jourdan, N., Saleun, S., Moullier, P., Duisit, G. (2002). Characterization of Producer Cell-Dependent Restriction of Murine Leukemia Virus Replication. J. Virol. 76: 6609-6617 [Abstract] [Full Text]  
  • Crotty, S., Hix, L., Sigal, L. J., Andino, R. (2002). Poliovirus pathogenesis in a new poliovirus receptor transgenic mouse model: age-dependent paralysis and a mucosal route of infection. J. Gen. Virol. 83: 1707-1720 [Abstract] [Full Text]  
  • Zhang, Y.-j., Hatziioannou, T., Zang, T., Braaten, D., Luban, J., Goff, S. P., Bieniasz, P. D. (2002). Envelope-Dependent, Cyclophilin-Independent Effects of Glycosaminoglycans on Human Immunodeficiency Virus Type 1 Attachment and Infection. J. Virol. 76: 6332-6343 [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]  
  • Reed, M., Mariani, R., Sheppard, L., Pekrun, K., Landau, N. R., Soong, N.-W. (2002). Chimeric Human Immunodeficiency Virus Type 1 Containing Murine Leukemia Virus Matrix Assembles in Murine Cells. J. Virol. 76: 436-443 [Abstract] [Full Text]  
  • Chen, B. K., Rousso, I., Shim, S., Kim, P. S. (2001). Efficient assembly of an HIV-1/MLV Gag-chimeric virus in murine cells. Proc. Natl. Acad. Sci. USA 10.1073/pnas.261563198v1 [Abstract] [Full Text]  
  • Deml, L., Bojak, A., Steck, S., Graf, M., Wild, J., Schirmbeck, R., Wolf, H., Wagner, R. (2001). Multiple Effects of Codon Usage Optimization on Expression and Immunogenicity of DNA Candidate Vaccines Encoding the Human Immunodeficiency Virus Type 1 Gag Protein. J. Virol. 75: 10991-11001 [Abstract] [Full Text]  
  • Keppler, O. T., Yonemoto, W., Welte, F. J., Patton, K. S., Iacovides, D., Atchison, R. E., Ngo, T., Hirschberg, D. L., Speck, R. F., Goldsmith, M. A. (2001). Susceptibility of Rat-Derived Cells to Replication by Human Immunodeficiency Virus Type 1. J. Virol. 75: 8063-8073 [Abstract] [Full Text]  
  • Reid, W., Sadowska, M., Denaro, F., Rao, S., Foulke, J. Jr., Hayes, N., Jones, O., Doodnauth, D., Davis, H., Sill, A., O'Driscoll, P., Huso, D., Fouts, T., Lewis, G., Hill, M., Kamin-Lewis, R., Wei, C., Ray, P., Gallo, R. C., Reitz, M., Bryant, J. (2001). From the Cover: An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction. Proc. Natl. Acad. Sci. USA 98: 9271-9276 [Abstract] [Full Text]  
  • Tritel, M., Resh, M. D. (2001). The Late Stage of Human Immunodeficiency Virus Type 1 Assembly Is an Energy-Dependent Process. J. Virol. 75: 5473-5481 [Abstract] [Full Text]  
  • Coburn, G. A., Wiegand, H. L., Kang, Y., Ho, D. N., Georgiadis, M. M., Cullen, B. R. (2001). Using viral species specificity to define a critical protein/RNA interaction surface. Genes Dev. 15: 1194-1205 [Abstract] [Full Text]  
  • Mariani, R., Rasala, B. A., Rutter, G., Wiegers, K., Brandt, S. M., Kräusslich, H.-G., Landau, N. R. (2001). Mouse-Human Heterokaryons Support Efficient Human Immunodeficiency Virus Type 1 Assembly. J. Virol. 75: 3141-3151 [Abstract] [Full Text]  
  • Chen, B. K., Rousso, I., Shim, S., Kim, P. S. (2001). Efficient assembly of an HIV-1/MLV Gag-chimeric virus in murine cells. Proc. Natl. Acad. Sci. USA 98: 15239-15244 [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»