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

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.
Mesh Terms:
Alleles, Amino Acid Sequence, Apoptosis, Gene Products, vpr, Genes, vpr, Genetic Variation, Humans, Leukocytes, Mononuclear, Models, Genetic, Molecular Sequence Data, Mutation, Protein Binding, Terminal Repeat Sequences, Ubiquitin-Protein Ligases, vpr Gene Products, Human Immunodeficiency Virus
PLoS ONE
Date: Oct. 20, 2009
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