Open AccessThe First HxRxG Motif in Simian Immunodeficiency Virus mac239 Vpr Is Crucial for G 2 /M Cell Cycle Arrest
Author(s) -
Sandra Mueller,
Sabine M. Lang
Publication year - 2002
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.76.22.11704-11709.2002
Subject(s) - transactivation , biology , cell cycle checkpoint , simian immunodeficiency virus , cell cycle , mutant , microbiology and biotechnology , mutation , nuclear transport , virus , virology , cell , genetics , cell nucleus , transcription factor , nucleus , gene
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 alpha-helical region and two C-terminal HxRxG motifs. All Vpr mutants located to the nucleus. Substitution of four amino acids in the alpha-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 G(2)/M mediates or contributes to transactivation by Vpr.