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 Anderson, J. L.
Right arrow Articles by Hope, T. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Anderson, J. L.
Right arrow Articles by Hope, T. J.

 Previous Article  |  Next Article 

Journal of Virology, October 2006, p. 9754-9760, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.01052-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Proteasome Inhibition Reveals that a Functional Preintegration Complex Intermediate Can Be Generated during Restriction by Diverse TRIM5 Proteins

Jenny L. Anderson,1,{dagger} Edward M. Campbell,1,{dagger} Xiaolu Wu,1,2 Nick Vandegraaff,3,4 Alan Engelman,3,4 and Thomas J. Hope1,2*

Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611,1 Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, Illinois 60612,2 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115,3 Department of Pathology, Harvard Medical School, Boston, Massachusetts 021154

Received 22 May 2006/ Accepted 8 July 2006

The primate TRIM5 proteins constitute a class of restriction factors that prevent host cell infection by retroviruses from different species. The TRIM5 proteins act early after virion entry and prevent viral reverse transcription products from accumulating. We recently found that proteasome inhibitors altered the rhesus monkey TRIM5{alpha} restriction of human immunodeficiency virus type 1 (HIV-1), allowing reverse transcription products to accumulate even though viral infection remained blocked. To assess whether sensitivity to proteasome inhibitors was a common feature of primate TRIM5 proteins, we conducted a similar analysis of restriction mediated by owl monkey TRIM-cyclophilin A (CypA) or human TRIM5{alpha}. Similar to rhesus monkey TRIM5{alpha} restriction, proteasome inhibition prevented owl monkey TRIM-CypA restriction of HIV-1 reverse transcription, even though HIV-1 infection and the output of 2-LTR circles remained impaired. Likewise, proteasome inhibition alleviated human TRIM5{alpha} restriction of N-tropic murine leukemia virus reverse transcription. Finally, HIV-1 reverse transcription products escaping rhesus TRIM5{alpha} restriction by proteasome inhibition were fully competent for integration in vitro, demonstrating that TRIM5{alpha} likely prevents the viral cDNA from accessing chromosomal target DNA. Collectively, these data indicate that the diverse TRIM5 proteins inhibit retroviral infection in multiple ways and that inhibition of reverse transcription products is not necessary for TRIM5-mediated restriction of retroviral infection.

* Corresponding author. Mailing address: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Ward 8-140, 303 East Chicago Avenue, Chicago, IL 60611. Phone: (312) 503-1360. Fax: (312) 503-2696. E-mail: thope{at}northwestern.edu.

{dagger} These authors contributed equally to this work.

Journal of Virology, October 2006, p. 9754-9760, Vol. 80, No. 19
0022-538X/06/$08.00+0     doi:10.1128/JVI.01052-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Yamashita, M., Emerman, M. (2009). Cellular Restriction Targeting Viral Capsids Perturbs Human Immunodeficiency Virus Type 1 Infection of Nondividing Cells. J. Virol. 83: 9835-9843 [Abstract] [Full Text]  
  • McEwan, W. A., Schaller, T., Ylinen, L. M., Hosie, M. J., Towers, G. J., Willett, B. J. (2009). Truncation of TRIM5 in the Feliformia Explains the Absence of Retroviral Restriction in Cells of the Domestic Cat. J. Virol. 83: 8270-8275 [Abstract] [Full Text]  
  • Wood, A., Webb, B. L. J., Bartosch, B., Schaller, T., Takeuchi, Y., Towers, G. J. (2009). Porcine endogenous retroviruses PERV A and A/C recombinant are insensitive to a range of divergent mammalian TRIM5{alpha} proteins including human TRIM5{alpha}. J. Gen. Virol. 90: 702-709 [Abstract] [Full Text]  
  • Langelier, C. R., Sandrin, V., Eckert, D. M., Christensen, D. E., Chandrasekaran, V., Alam, S. L., Aiken, C., Olsen, J. C., Kar, A. K., Sodroski, J. G., Sundquist, W. I. (2008). Biochemical Characterization of a Recombinant TRIM5{alpha} Protein That Restricts Human Immunodeficiency Virus Type 1 Replication. J. Virol. 82: 11682-11694 [Abstract] [Full Text]  
  • Li, X., Sodroski, J. (2008). The TRIM5{alpha} B-Box 2 Domain Promotes Cooperative Binding to the Retroviral Capsid by Mediating Higher-Order Self-Association. J. Virol. 82: 11495-11502 [Abstract] [Full Text]  
  • Richardson, M. W., Carroll, R. G., Stremlau, M., Korokhov, N., Humeau, L. M., Silvestri, G., Sodroski, J., Riley, J. L. (2008). Mode of Transmission Affects the Sensitivity of Human Immunodeficiency Virus Type 1 to Restriction by Rhesus TRIM5{alpha}. J. Virol. 82: 11117-11128 [Abstract] [Full Text]  
  • Diehl, W. E., Stansell, E., Kaiser, S. M., Emerman, M., Hunter, E. (2008). Identification of Postentry Restrictions to Mason-Pfizer Monkey Virus Infection in New World Monkey Cells. J. Virol. 82: 11140-11151 [Abstract] [Full Text]  
  • Yap, M. W., Lindemann, D., Stanke, N., Reh, J., Westphal, D., Hanenberg, H., Ohkura, S., Stoye, J. P. (2008). Restriction of Foamy Viruses by Primate Trim5{alpha}. J. Virol. 82: 5429-5439 [Abstract] [Full Text]  
  • Galla, M., Schambach, A., Towers, G. J., Baum, C. (2008). Cellular Restriction of Retrovirus Particle-Mediated mRNA Transfer. J. Virol. 82: 3069-3077 [Abstract] [Full Text]  
  • Wilson, S. J., Webb, B. L. J., Ylinen, L. M. J., Verschoor, E., Heeney, J. L., Towers, G. J. (2008). From the Cover: Independent evolution of an antiviral TRIMCyp in rhesus macaques. Proc. Natl. Acad. Sci. USA 105: 3557-3562 [Abstract] [Full Text]  
  • Anderson, J. L., Campbell, E. M., Figueiredo, A., Hope, T. J. (2008). Heat Shock Perturbs TRIM5{alpha} Restriction of Human Immunodeficiency Virus Type 1. J. Virol. 82: 2575-2579 [Abstract] [Full Text]  
  • Campbell, E. M., Perez, O., Anderson, J. L., Hope, T. J. (2008). Visualization of a proteasome-independent intermediate during restriction of HIV-1 by rhesus TRIM5{alpha}. JCB 180: 549-561 [Abstract] [Full Text]  
  • Schaller, T., Hue, S., Towers, G. J. (2007). An Active TRIM5 Protein in Rabbits Indicates a Common Antiviral Ancestor for Mammalian TRIM5 Proteins. J. Virol. 81: 11713-11721 [Abstract] [Full Text]  
  • Schaller, T., Ylinen, L. M. J., Webb, B. L. J., Singh, S., Towers, G. J. (2007). Fusion of Cyclophilin A to Fv1 Enables Cyclosporine-Sensitive Restriction of Human and Feline Immunodeficiency Viruses. J. Virol. 81: 10055-10063 [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»