Global post-translational modification profiling of HIV-1-infected cells reveals mechanisms of host cellular pathway remodeling

Jeffrey R. Johnson, David C. Crosby, Judd F. Hultquist, Andrew P. Kurland, Prithy Adhikary, Donna Li, John Marlett, Justine Swann, Ruth Hüttenhain, Erik Verschueren, Tasha L. Johnson, Billy W. Newton, Michael Shales, Viviana A. Simon, Pedro Beltrao, Alan D. Frankel, Alexander Marson, Jeffery S. Cox, Oliver I. Fregoso, John A.T. YoungNevan J. Krogan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Viruses must effectively remodel host cellular pathways to replicate and evade immune defenses, and they must do so with limited genomic coding capacity. Targeting post-translational modification (PTM) pathways provides a mechanism by which viruses can broadly and rapidly transform a hostile host environment into a hospitable one. We use mass spectrometry-based proteomics to quantify changes in protein abundance and two PTM types—phosphorylation and ubiquitination—in response to HIV-1 infection with viruses harboring targeted deletions of a subset of HIV-1 genes. PTM analysis reveals a requirement for Aurora kinase activity in HIV-1 infection and identified putative substrates of a phosphatase that is degraded during infection. Finally, we demonstrate that the HIV-1 Vpr protein inhibits histone H1 ubiquitination, leading to defects in DNA repair.

Original languageEnglish
Article number110690
JournalCell Reports
Volume39
Issue number2
DOIs
StatePublished - 12 Apr 2022

Keywords

  • CP: Microbiology
  • CP: Molecular biology
  • HIV-1
  • b56
  • histone h1
  • phosphorylation
  • pp2a
  • proteomics
  • systems biology
  • ubiquitination
  • vif
  • vpr

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