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Journal of Virology, September 2008, p. 9265-9272, Vol. 82, No. 18
0022-538X/08/$08.00+0     doi:10.1128/JVI.00377-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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{triangledown} ,{ddagger}

Jason L. DeHart,1,{dagger} Alberto Bosque,1,{dagger} Reuben S. Harris,2 and Vicente Planelles1*

Division of Cellular Biology and Immunology, Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East no. 2100, Room 2520, Salt Lake City, Utah 84112,1 Biochemistry, Molecular Biology and Biophysics Department, University of Minnesota, 321 Church Street South East, 6-155 Jackson Hall, Minneapolis, Minnesota 554552

Received 21 February 2008/ Accepted 27 June 2008

Human immunodeficiency virus type 1 (HIV-1) Vif recruits a Cullin 5 ubiquitin ligase that targets APOBEC3 proteins for degradation. Recently, Vif has also been shown to induce cell cycle disturbance in G2. We show that in contrast to the expression of Vpr, the expression of Vif does not preclude cell division, and therefore, Vif causes delay and not arrest in G2. We also demonstrate that the interaction of Vif with the ubiquitin ligase is required for cell cycle disruption, as was previously shown for HIV-1 Vpr. The presence of APOBEC3 D/E, F, and G had no influence on Vif-induced alteration of the cell cycle. We conclude that cell cycle delay by Vif is a result of ubiquitination and degradation of a cellular protein that is different from the known APOBEC3 family members.


* Corresponding author. Mailing address: Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East no. 2100, Room 2520, Salt Lake City, Utah 84112. Phone: (801) 581-8655. Fax: (801) 587-7799. E-mail: vicente.planelles{at}path.utah.edu

{triangledown} Published ahead of print on 2 July 2008.

{ddagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{dagger} These authors contributed equally.


Journal of Virology, September 2008, p. 9265-9272, Vol. 82, No. 18
0022-538X/08/$08.00+0     doi:10.1128/JVI.00377-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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