Determinants for degradation of SAMHD1, Mus81 and induction of G2 arrest in HIV-1 Vpr and SIVagm Vpr

Virology. 2015 Mar;477:10-17. doi: 10.1016/j.virol.2014.12.040. Epub 2015 Jan 22.

Abstract

Vpr and Vpx are a group of highly related accessory proteins from primate lentiviruses. Despite the high degree of amino acid homology within this group, these proteins can be highly divergent in their functions. In this work, we constructed chimeric and mutant proteins between HIV-1 and SIVagm Vpr in order to better understand the structure-function relationships. We tested these constructs for their abilities to induce G2 arrest in human cells and to degrade agmSAMHD1 and Mus81. We found that the C-terminus of HIV-1 Vpr, when transferred onto SIVagm Vpr, provides the latter with the de novo ability to induce G2 arrest in human cells. We confirmed that HIV-1 Vpr induces degradation of Mus81 although, surprisingly, degradation is independent and genetically separable from Vpr׳s ability to induce G2 arrest.

Keywords: Agm; DCAF1; G2 arrest; HIV-1; MLN4924; Mus81; SAMHD1; SIV; Ubiquitination; Vpr.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Cycle*
  • DNA-Binding Proteins / metabolism*
  • Endonucleases / metabolism*
  • Gene Products, vpr / genetics
  • Gene Products, vpr / metabolism*
  • HIV-1 / physiology*
  • HeLa Cells
  • Host-Pathogen Interactions*
  • Humans
  • Monomeric GTP-Binding Proteins / metabolism*
  • Proteolysis
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • SAM Domain and HD Domain-Containing Protein 1
  • Simian Immunodeficiency Virus / physiology*

Substances

  • DNA-Binding Proteins
  • Gene Products, vpr
  • Recombinant Proteins
  • Endonucleases
  • MUS81 protein, human
  • SAM Domain and HD Domain-Containing Protein 1
  • SAMHD1 protein, human
  • Monomeric GTP-Binding Proteins