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Journal of Virology, April 2006, p. 3694-3700, Vol. 80, No. 8
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.8.3694-3700.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Induction of G2 Arrest and Binding to Cyclophilin A Are Independent Phenotypes of Human Immunodeficiency Virus Type 1 Vpr

Orly Ardon, Erik S. Zimmerman, Joshua L. Andersen, Jason L. DeHart, Jana Blackett, and Vicente Planelles*

Division of Cellular Biology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84132

Received 26 November 2005/ Accepted 25 January 2006

Cyclophilin A (CypA) is a member of a family of cellular proteins that share a peptidyl prolyl cis-trans isomerase (PPIase) activity. CypA was previously reported to be required for the biochemical stability and function (specifically, induction of G2 arrest) of the human immunodeficiency virus type 1 (HIV-1) protein R (Vpr). In the present study, we examine the role of the Vpr-CypA interaction on Vpr-induced G2 arrest. We find that Vpr coimmunoprecipitates with CypA and that this interaction is disrupted by substitution of proline-35 of Vpr as well as incubation with the CypA inhibitor cyclosporine A (CsA). Surprisingly, the presence of CypA or its binding to Vpr is dispensable for the ability of Vpr to induce G2 arrest. Vpr expression in CypA–/– cells leads to induction of G2 arrest in a manner that is indistinguishable from that in CypA+ cells. CsA abolished CypA-Vpr binding but had no effect on induction of G2 arrest or Vpr steady-state levels. In view of these results, we propose that the interaction with CypA is independent of the ability of Vpr to induce cell cycle arrest. The interaction between Vpr and CypA is intriguing, and further studies should examine its potential effects on other functions of Vpr.


* Corresponding author. Mailing address: Department of Pathology, University of Utah School of Medicine, 30 N 1900 East, SOM 5C210, Salt Lake City, UT 84132. Phone: (801) 581-8655. Fax: (801) 587-7799. E-mail: vicente.planelles{at}path.utah.edu.


Journal of Virology, April 2006, p. 3694-3700, Vol. 80, No. 8
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.8.3694-3700.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • DeHart, J. L., Bosque, A., Harris, R. S., Planelles, V. (2008). Human Immunodeficiency Virus Type 1 Vif Induces Cell Cycle Delay via Recruitment of the Same E3 Ubiquitin Ligase Complex That Targets APOBEC3 Proteins for Degradation. J. Virol. 82: 9265-9272 [Abstract] [Full Text]  
  • Zimmerman, E. S., Sherman, M. P., Blackett, J. L., Neidleman, J. A., Kreis, C., Mundt, P., Williams, S. A., Warmerdam, M., Kahn, J., Hecht, F. M., Grant, R. M., de Noronha, C. M. C., Weyrich, A. S., Greene, W. C., Planelles, V. (2006). Human Immunodeficiency Virus Type 1 Vpr Induces DNA Replication Stress In Vitro and In Vivo. J. Virol. 80: 10407-10418 [Abstract] [Full Text]