Evolutionary and functional analyses of the interaction between the myeloid restriction factor SAMHD1 and the lentiviral Vpx protein.
SAMHD1 has recently been identified as an HIV-1 restriction factor operating in myeloid cells. As a countermeasure, the Vpx accessory protein from HIV-2 and certain lineages of SIV have evolved to antagonize SAMHD1 by inducing its ubiquitin-proteasome-dependent degradation. Here, we show that SAMHD1 experienced strong positive selection episodes during primate evolution that occurred in the Catarrhini ancestral branch prior to the separation between hominoids (gibbons and great apes) and Old World monkeys. The identification of SAMHD1 residues under positive selection led to mapping the Vpx-interaction domain of SAMHD1 to its C-terminal region. Importantly, we found that while SAMHD1 restriction activity toward HIV-1 is evolutionarily maintained, antagonism of SAMHD1 by Vpx is species-specific. The distinct evolutionary signature of SAMHD1 sheds light on the development of its antiviral specificity.
Institut de Génétique Humaine, Centre National de la Recherche Scientifique, Unité Propre de Recherche 1142, Laboratoires de Virologie Moléculaire, 34000 Montpellier, France.
Nadine
N
Laguette
Nadia
N
Rahm
Bijan
B
Sobhian
Christine
C
Chable-Bessia
Jan
J
Münch
Joke
J
Snoeck
Daniel
D
Sauter
William M
WM
Switzer
Walid
W
Heneine
Frank
F
Kirchhoff
Frédéric
F
Delsuc
Amalio
A
Telenti
Monsef
M
Benkirane
D000818:Animals; D001665:Binding Sites; D016000:Cluster Analysis; D019143:Evolution, Molecular; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D015498:HIV-2 / Q000276:immunology / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D010802:Phylogeny; D011323:Primates; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017386:Sequence Homology, Amino Acid; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics* / Q000378:metabolism*
C074286:VPX protein, Human immunodeficiency virus 2; D054334:Viral Regulatory and Accessory Proteins; D020559:Monomeric GTP-Binding Proteins