The ability of primate lentiviruses to degrade the monocyte restriction factor SAMHD1 preceded the birth of the viral accessory protein Vpx.

Abstract	The human SAMHD1 protein potently restricts lentiviral infection in dendritic cells and monocyte/macrophages but is antagonized by the primate lentiviral protein Vpx, which targets SAMHD1 for degradation. However, only two of eight primate lentivirus lineages encode Vpx, whereas its paralog, Vpr, is conserved across all extant primate lentiviruses. We find that not only multiple Vpx but also some Vpr proteins are able to degrade SAMHD1, and such antagonism led to dramatic positive selection of SAMHD1 in the primate subfamily Cercopithecinae. Residues that have evolved under positive selection precisely determine sensitivity to Vpx/Vpr degradation and alter binding specificity. By overlaying these functional analyses on a phylogenetic framework of Vpr and Vpx evolution, we can decipher the chronology of acquisition of SAMHD1-degrading abilities in lentiviruses. We conclude that vpr neofunctionalized to degrade SAMHD1 even prior to the birth of a separate vpx gene, thereby initiating an evolutionary arms race with SAMHD1.
Authors	Efrem S Lim, Oliver I Fregoso, Connor O McCoy, Frederick A Matsen, Harmit S Malik, Michael Emerman
Journal	Cell host & microbe (Cell Host Microbe) Vol. 11 Issue 2 Pg. 194-204 (Feb 16 2012) ISSN: 1934-6069 [Electronic] United States
PMID	22284954 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Copyright	Copyright Â© 2012 Elsevier Inc. All rights reserved.
Chemical References	Viral Regulatory and Accessory Proteins Monomeric GTP-Binding Proteins
Topics	Amino Acid Sequence Animals Cell Line Cercopithecinae (genetics, immunology, virology) Cluster Analysis Evolution, Molecular Host-Pathogen Interactions Humans Lentiviruses, Primate (genetics, pathogenicity) Molecular Sequence Data Monomeric GTP-Binding Proteins (genetics, immunology, metabolism) Phylogeny Proteolysis Sequence Analysis, DNA Sequence Homology, Amino Acid Viral Regulatory and Accessory Proteins (genetics, metabolism)

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