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 Saphire, A. C. S.
Right arrow Articles by Gallay, P. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Saphire, A. C. S.
Right arrow Articles by Gallay, P. A.

 Previous Article  |  Next Article 

Journal of Virology, March 2002, p. 2255-2262, Vol. 76, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/jvi.76.5.2255-2262.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

trans-Complementation Rescue of Cyclophilin A-Deficient Viruses Reveals that the Requirement for Cyclophilin A in Human Immunodeficiency Virus Type 1 Replication Is Independent of Its Isomerase Activity{dagger}

*** Andrew C. S. Saphire, Michael D. Bobardt, and Philippe A. Gallay*

Department of Immunology, The Scripps Research Institute, La Jolla, California 92037

Received 9 July 2001/ Accepted 5 December 2001

Human immunodeficiency virus type 1 (HIV-1) requires the incorporation of cyclophilin A (CypA) for replication. CypA is packaged by binding to the capsid (CA) region of Gag. This interaction is disrupted by cyclosporine (CsA). Preventing CypA incorporation, either by mutations in the binding region of CA or by the presence of CsA, abrogates virus infectivity. Given that CypA possesses an isomerase activity, it has been proposed that CypA acts as an uncoating factor by destabilizing the shell of CA that surrounds the viral genome. However, because the same domain of CypA is responsible for both its isomerase activity and its capacity to be packaged, it has been challenging to determine if isomerase activity is required for HIV-1 replication. To address this issue, we fused CypA to viral protein R (Vpr), creating a Vpr-CypA chimera. Because Vpr is packaged via the p6 region of Gag, this approach bypasses the interaction with CA and allows CypA incorporation even in the presence of CsA. Using this system, we found that Vpr-CypA rescues the infectivity of viruses lacking CypA, either produced in the presence of CsA or mutated in the CypA packaging signal of CA. Furthermore, a Vpr-CypA mutant which has no isomerase activity and no capacity to bind to CA also rescues HIV-1 replication. Thus, this study demonstrates that the isomerase activity of CypA is not required for HIV-1 replication and suggests that the interaction of the catalytic site of CypA with CA serves no other function than to incorporate CypA into viruses.

* Corresponding author. Mailing address: Department of Immunology IMM-9, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-8180. Fax: (858) 784-8227. E-mail: gallay{at}scripps.edu.

{dagger} Publication no. 14250-IMM from the Department of Immunology, The Scripps Research Institute, La Jolla, Calif.

Journal of Virology, March 2002, p. 2255-2262, Vol. 76, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/jvi.76.5.2255-2262.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Li, Y., Kar, A. K., Sodroski, J. (2009). Target Cell Type-Dependent Modulation of Human Immunodeficiency Virus Type 1 Capsid Disassembly by Cyclophilin A. J. Virol. 83: 10951-10962 [Abstract] [Full Text]  
  • Cantin, R., Methot, S., Tremblay, M. J. (2005). Plunder and Stowaways: Incorporation of Cellular Proteins by Enveloped Viruses. J. Virol. 79: 6577-6587 [Full Text]  
  • Chen, Z.-J., Vetter, M., Chang, G.-D., Liu, S., Che, D., Ding, Y., Kim, S. S., Chang, C.-H. (2004). Cyclophilin A Functions as an Endogenous Inhibitor for Membrane-Bound Guanylate Cyclase-A. Hypertension 44: 963-968 [Abstract] [Full Text]  
  • Wang, H.-H., Yu, H.-H., Wong, S.-M. (2004). Mutation of Phe50 to Ser50 in the 126/183-kDa proteins of Odontoglossum ringspot virus abolishes virus replication but can be complemented and restored by exact reversion. J. Gen. Virol. 85: 2447-2457 [Abstract] [Full Text]  
  • Narayan, S., Young, J. A. T. (2004). Reconstitution of retroviral fusion and uncoating in a cell-free system. Proc. Natl. Acad. Sci. USA 101: 7721-7726 [Abstract] [Full Text]  
  • Khan, M., Jin, L., Huang, M. B., Miles, L., Bond, V. C., Powell, M. D. (2004). Chimeric Human Immunodeficiency Virus Type 1 (HIV-1) Virions Containing HIV-2 or Simian Immunodeficiency Virus Nef Are Resistant to Cyclosporine Treatment. J. Virol. 78: 1843-1850 [Abstract] [Full Text]  
  • Schubert, A., Grimm, S. (2004). Cyclophilin D, a Component of the Permeability Transition-Pore, Is an Apoptosis Repressor. Cancer Res. 64: 85-93 [Abstract] [Full Text]  
  • Zander, K., Sherman, M. P., Tessmer, U., Bruns, K., Wray, V., Prechtel, A. T., Schubert, E., Henklein, P., Luban, J., Neidleman, J., Greene, W. C., Schubert, U. (2003). Cyclophilin A Interacts with HIV-1 Vpr and Is Required for Its Functional Expression. J. Biol. Chem. 278: 43202-43213 [Abstract] [Full Text]  
  • Khan, M., Garcia-Barrio, M., Powell, M. D. (2003). Treatment of Human Immunodeficiency Virus Type 1 Virions Depleted of Cyclophilin A by Natural Endogenous Reverse Transcription Restores Infectivity. J. Virol. 77: 4431-4434 [Abstract] [Full Text]  
  • Saphire, A. C. S., Bobardt, M. D., Gallay, P. A. (2002). Cyclophilin A Plays Distinct Roles in Human Immunodeficiency Virus Type 1 Entry and Postentry Events, as Revealed by Spinoculation. J. Virol. 76: 4671-4677 [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»