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

Efrem Lim, Oliver I. Fregoso, Connor O. McCoy, Frederick A. Matsen, Harmit S. Malik, Michael Emerman

Research output: Contribution to journalArticle

168 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)194-204
Number of pages11
JournalCell Host and Microbe
Volume11
Issue number2
DOIs
StatePublished - Feb 16 2012
Externally publishedYes

Fingerprint

Viral Regulatory and Accessory Proteins
Primate Lentiviruses
Cercopithecinae
Primates
Monocytes
vpr Gene Products
Parturition
Chronology
Lentivirus
Dendritic Cells
Macrophages
Infection
Genes
Proteins

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

The ability of primate lentiviruses to degrade the monocyte restriction factor SAMHD1 preceded the birth of the viral accessory protein Vpx. / Lim, Efrem; Fregoso, Oliver I.; McCoy, Connor O.; Matsen, Frederick A.; Malik, Harmit S.; Emerman, Michael.

In: Cell Host and Microbe, Vol. 11, No. 2, 16.02.2012, p. 194-204.

Research output: Contribution to journalArticle

Lim, Efrem ; Fregoso, Oliver I. ; McCoy, Connor O. ; Matsen, Frederick A. ; Malik, Harmit S. ; Emerman, Michael. / The ability of primate lentiviruses to degrade the monocyte restriction factor SAMHD1 preceded the birth of the viral accessory protein Vpx. In: Cell Host and Microbe. 2012 ; Vol. 11, No. 2. pp. 194-204.
@article{ef439b8b068a4f2b8f90a6908f8798da,
title = "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.",
author = "Efrem Lim and Fregoso, {Oliver I.} and McCoy, {Connor O.} and Matsen, {Frederick A.} and Malik, {Harmit S.} and Michael Emerman",
year = "2012",
month = "2",
day = "16",
doi = "10.1016/j.chom.2012.01.004",
language = "English (US)",
volume = "11",
pages = "194--204",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - The ability of primate lentiviruses to degrade the monocyte restriction factor SAMHD1 preceded the birth of the viral accessory protein Vpx

AU - Lim, Efrem

AU - Fregoso, Oliver I.

AU - McCoy, Connor O.

AU - Matsen, Frederick A.

AU - Malik, Harmit S.

AU - Emerman, Michael

PY - 2012/2/16

Y1 - 2012/2/16

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84857347109&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84857347109&partnerID=8YFLogxK

U2 - 10.1016/j.chom.2012.01.004

DO - 10.1016/j.chom.2012.01.004

M3 - Article

C2 - 22284954

AN - SCOPUS:84857347109

VL - 11

SP - 194

EP - 204

JO - Cell Host and Microbe

JF - Cell Host and Microbe

SN - 1931-3128

IS - 2

ER -