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.
Institut Cochin, Université Paris-Descartes, CNRS, UMR 8104, Paris, France.
Guillaume
G
Jacquot
Erwann
E
Le Rouzic
Priscilla
P
Maidou-Peindara
Marion
M
Maizy
Jean-Jacques
JJ
Lefrère
Vincent
V
Daneluzzi
Carlos M R
CM
Monteiro-Filho
Duanping
D
Hong
Vicente
V
Planelles
Laurence
L
Morand-Joubert
Serge
S
Benichou
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