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The First HxRxG Motif in Simian Immunodeficiency Virus mac239 Vpr Is Crucial for G2/M Cell Cycle Arrest

Authors
Publisher
American Society for Microbiology
Publication Date
Source
PMC
Keywords
  • Virus-Cell Interactions
Disciplines
  • Biology

Abstract

The highly conserved Vpr protein mediates cell cycle arrest, transcriptional transactivation, and nuclear import of the preintegration complex in human immunodeficiency virus type 1. To identify functional domains in simian immunodeficiency virus (SIV) mac239 Vpr, we mutagenized selected motifs within an α-helical region and two C-terminal HxRxG motifs. All Vpr mutants located to the nucleus. Substitution of four amino acids in the α-helical domain did not interfere with cell cycle arrest, while a single substitution abolished cell cycle arrest function. Mutation of the first HxRxG motif to AxAxA also resulted in loss of cell cycle arrest, while mutation of the second motif had no effect. Interestingly, both Vpr mutants impaired in cell cycle arrest function also showed reduced transactivation of the SIV long terminal repeat, suggesting that arrest of cells at G2/M mediates or contributes to transactivation by Vpr.

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