Interaction of human immunodeficiency virus type 1 Vpr with the HHR23A DNArepair protein does not correlate with multiple biological functions of Vpr

Citation
Lm. Mansky et al., Interaction of human immunodeficiency virus type 1 Vpr with the HHR23A DNArepair protein does not correlate with multiple biological functions of Vpr, VIROLOGY, 282(1), 2001, pp. 176-185
Citations number
31
Categorie Soggetti
Microbiology
Journal title
VIROLOGY
ISSN journal
00426822 → ACNP
Volume
282
Issue
1
Year of publication
2001
Pages
176 - 185
Database
ISI
SICI code
0042-6822(20010330)282:1<176:IOHIVT>2.0.ZU;2-U
Abstract
The virion-associated Vpr protein of human immunodeficiency virus type 1 (H IV-1) alters cell cycle progression from the G2 phase, influences the virus in vivo mutation rate, and participates in the nuclear translocation of vi ral DNA. While many Vpr-interacting proteins have been identified, the func tional relevance of these interactions remains to be thoroughly documented. We have explored the contribution of the interaction of HIV-1 Vpr with HHR 23A, a cellular protein implicated in DNA repair, to the known phenotypes o f Vpr. The association of Vpr with HHR23A required the core region of Vpr, which encompasses the two alpha-helical structures of the protein. No bindi ng of HHR23A was detected with the Vpr and Vpx proteins of other primate le ntiviruses. HIV-1 Vpr variants containing single amino acid substitutions i n each alpha-helix and deficient for binding to HHR23A were isolated. The f unctional characterization of these Vpr variants indicated that binding to HHR23A did not correlate with the ability of Vpr to induce cell cycle arres t, even though it was previously proposed that HHR23A is a mediator of the Vpr-induced G2 arrest. Also, the Vpr-HHR23A interaction did not influence t he HIV-1 in vivo mutation rate. Finally, Vpr and HHR23A are both localized in the nucleus, but no correlation was observed between the nuclear targeti ng of Vpr and the interaction with HHR23A. Further analysis is needed to de termine the functional role(s) of the Vpr-HHR23A association during the HIV -1 life cycle. (C) 2001 Academic Press.