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

Cell Host Microbe. 2012 Feb 16;11(2):194-204. doi: 10.1016/j.chom.2012.01.004. Epub 2012 Jan 26.


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.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cercopithecinae / genetics*
  • Cercopithecinae / immunology
  • Cercopithecinae / virology
  • Cluster Analysis
  • Evolution, Molecular*
  • Host-Pathogen Interactions*
  • Humans
  • Lentiviruses, Primate / genetics*
  • Lentiviruses, Primate / pathogenicity
  • Molecular Sequence Data
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / immunology
  • Monomeric GTP-Binding Proteins / metabolism*
  • Phylogeny
  • Proteolysis
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Viral Regulatory and Accessory Proteins / genetics*
  • Viral Regulatory and Accessory Proteins / metabolism


  • Viral Regulatory and Accessory Proteins
  • Monomeric GTP-Binding Proteins

Associated data

  • GENBANK/JQ231123
  • GENBANK/JQ231124
  • GENBANK/JQ231125
  • GENBANK/JQ231126
  • GENBANK/JQ231127
  • GENBANK/JQ231128
  • GENBANK/JQ231129
  • GENBANK/JQ231130
  • GENBANK/JQ231131
  • GENBANK/JQ231132
  • GENBANK/JQ231133
  • GENBANK/JQ231134
  • GENBANK/JQ231135
  • GENBANK/JQ231136
  • GENBANK/JQ231137
  • GENBANK/JQ231138
  • GENBANK/JQ231139
  • GENBANK/JQ231140
  • GENBANK/JQ231141
  • GENBANK/JQ231142
  • GENBANK/JQ231143
  • GENBANK/JQ231144
  • GENBANK/JQ231145
  • GENBANK/JQ231146
  • GENBANK/JQ231147
  • GENBANK/JQ231148
  • GENBANK/JQ231149
  • GENBANK/JQ231150
  • GENBANK/JQ231151
  • GENBANK/JQ231152