Interaction of human immunodeficiency virus type 1 Vpr with the HHR23A DNA repair protein does not correlate with multiple biological functions of Vpr.
The virion-associated Vpr protein of human immunodeficiency virus type 1 (HIV-1) alters cell cycle progression from the G2 phase, influences the virus in vivo mutation rate, and participates in the nuclear translocation of viral DNA. While many Vpr-interacting proteins have been identified, the functional relevance of these interactions remains to be thoroughly documented. We have explored the contribution of the interaction of HIV-1 Vpr with HHR23A, a cellular protein implicated in DNA repair, to the known phenotypes of Vpr. The association of Vpr with HHR23A required the core region of Vpr, which encompasses the two alpha-helical structures of the protein. No binding of HHR23A was detected with the Vpr and Vpx proteins of other primate lentiviruses. HIV-1 Vpr variants containing single amino acid substitutions in each alpha-helix and deficient for binding to HHR23A were isolated. The functional characterization of these Vpr variants indicated that binding to HHR23A did not correlate with the ability of Vpr to induce cell cycle arrest, 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 the HIV-1 in vivo mutation rate. Finally, Vpr and HHR23A are both localized in the nucleus, but no correlation was observed between the nuclear targeting of Vpr and the interaction with HHR23A. Further analysis is needed to determine the functional role(s) of the Vpr-HHR23A association during the HIV-1 life cycle.
Mansky
L M
LM
Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University Medical Center, Columbus 43210, USA. mansky.3@osu.edu
Preveral
S
S
Le Rouzic
E
E
Bernard
L C
LC
Selig
L
L
Depienne
C
C
Benarous
R
R
Benichou
S
S
D019943:Amino Acid Substitution; D000818:Animals; D019556:COS Cells; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016336:Gene Products, vpr / Q000378:metabolism*; D005822:Genetic Vectors; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D012191:Retroviridae Proteins / Q000378:metabolism*; D014162:Transfection; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus
D004268:DNA-Binding Proteins; D016336:Gene Products, vpr; D012191:Retroviridae Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; C086985:RAD23A protein, human; D045643:DNA Repair Enzymes