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. © 2009 Jacquot et al.
Jacquot, G., Le Rouzic, E., Maidou-Peindara, P., Maizy, M., Lefrère, J. J., Daneluzzi, V., … Benichou, S. (2009). Characterization of the molecular determinants of primary HIV-1 Vpr proteins: Impact of the Q65R and R77Q substitutions on Vpr functions. PLoS ONE, 4(10). https://doi.org/10.1371/journal.pone.0007514