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

PLoS One. 2009 Oct 19;4(10):e7514. doi: 10.1371/journal.pone.0007514.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Apoptosis
  • Gene Products, vpr / genetics*
  • Genes, vpr*
  • Genetic Variation
  • Humans
  • Leukocytes, Mononuclear / cytology
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Protein Binding
  • Terminal Repeat Sequences*
  • Ubiquitin-Protein Ligases / metabolism
  • vpr Gene Products, Human Immunodeficiency Virus / genetics*

Substances

  • Gene Products, vpr
  • vpr Gene Products, Human Immunodeficiency Virus
  • vpr protein, Human immunodeficiency virus 1
  • Ubiquitin-Protein Ligases