Characterization of the molecular determinants of primary HIV-1 Vpr proteins: impact of the Q65R and R77Q substitutions on Vpr functions.

• Main Authors: Guillaume Jacquot, Erwann Le Rouzic, Priscilla Maidou-Peindara, Marion Maizy, Jean-Jacques Lefrère, Vincent Daneluzzi, Carlos M R Monteiro-Filho, Duanping Hong, Vicente Planelles, Laurence Morand-Joubert, Serge Benichou
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2009-10-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC2759284?pdf=render

Although HIV-1 Vpr displays several functions in vitro, limited information exists concerning their relevance during infection. Here, we characterized Vpr variants isolated from a rapid and a long-term non-progressor (LTNP). Interestingly, vpr alleles isolated from longitudinal samples of the LTNP revealed a dominant sequence that subsequently led to diversity similar to that observed in the progressor patient. Most of primary Vpr proteins accumulated at the nuclear envelope and interacted with host-cell partners of Vpr. They displayed cytostatic and proapoptotic activities, although a LTNP allele, harboring the Q65R substitution, failed to bind the DCAF1 subunit of the Cul4a/DDB1 E3 ligase and was inactive. This Q65R substitution correlated with impairment of Vpr docking at the nuclear envelope, raising the possibility of a functional link between this property and the Vpr cytostatic activity. In contradiction with published results, the R77Q substitution, found in LTNP alleles, did not influence Vpr proapoptotic activity.