HIV-1 Vif promotes the G1- to S-phase cell-cycle transition

Jiangfang Wang, Emma L. Reuschel, Jason M. Shackelford, Lauren Jeang, Debra K. Shivers, J. Alan Diehl, Xiao Fang Yu, Terri H. Finkel

Research output: Contribution to journalArticle

Abstract

HIV-1 depends on host-cell resources for replication, access to which may be limited to a particular phase of the cell cycle. The HIV-encoded proteins Vpr (viral protein R) and Vif (viral infectivity factor) arrest cells in the G 2 phase; however, alteration of other cell-cycle phases has not been reported.We show that Vif drives cells out of G1 and into the S phase. The effect of Vif on the G1-to-S transition is distinct from its effect on G2, because G2 arrest is Cullin5-dependent, whereas the G1-to-S progression is Cullin5-independent. Using mass spectrometry, we identified 2 novel cellular partners of Vif, Brd4 and Cdk9, both of which are known to regulate cell-cycle progression. We confirmed the interaction of Vif and Cdk9 by immunoprecipitation and Western blot, and showed that small interfering RNAs (siRNAs) specific for Cdk9 inhibit the Vif-mediated G1-to-S transition. These data suggest that Vif regulates early cell-cycle progression, with implications for infection and latency.

Original languageEnglish (US)
Pages (from-to)1260-1269
Number of pages10
JournalBlood
Volume117
Issue number4
DOIs
StatePublished - Jan 27 2011

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Wang, J., Reuschel, E. L., Shackelford, J. M., Jeang, L., Shivers, D. K., Diehl, J. A., Yu, X. F., & Finkel, T. H. (2011). HIV-1 Vif promotes the G1- to S-phase cell-cycle transition. Blood, 117(4), 1260-1269. https://doi.org/10.1182/blood-2010-06-289215