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.
Jacquot
Guillaume
G
Institut Cochin, Université Paris-Descartes, CNRS, UMR 8104, Paris, France.
Le Rouzic
Erwann
E
Maidou-Peindara
Priscilla
P
Maizy
Marion
M
Lefrère
Jean-Jacques
JJ
Daneluzzi
Vincent
V
Monteiro-Filho
Carlos M R
CM
Hong
Duanping
D
Planelles
Vicente
V
Morand-Joubert
Laurence
L
Benichou
Serge
S
D000483:Alleles; D000595:Amino Acid Sequence; D017209:Apoptosis; D016336:Gene Products, vpr / Q000235:genetics*; D016334:Genes, vpr; D014644:Genetic Variation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D020079:Terminal Repeat Sequences; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1; D044767:Ubiquitin-Protein Ligases