@article{0d0ec7ac16ac4aa1a30519e8e345cf4f,
title = "Global post-translational modification profiling of HIV-1-infected cells reveals mechanisms of host cellular pathway remodeling",
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.",
keywords = "CP: Microbiology, CP: Molecular biology, HIV-1, b56, histone h1, phosphorylation, pp2a, proteomics, systems biology, ubiquitination, vif, vpr",
author = "Johnson, {Jeffrey R.} and Crosby, {David C.} and Hultquist, {Judd F.} and Kurland, {Andrew P.} and Prithy Adhikary and Donna Li and John Marlett and Justine Swann and Ruth H{\"u}ttenhain and Erik Verschueren and Johnson, {Tasha L.} and Newton, {Billy W.} and Michael Shales and Simon, {Viviana A.} and Pedro Beltrao and Frankel, {Alan D.} and Alexander Marson and Cox, {Jeffery S.} and Fregoso, {Oliver I.} and Young, {John A.T.} and Krogan, {Nevan J.}",
note = "Funding Information: This research was funded by grants from the National Institutes of Health ( P50 AI150476 , U19 AI135990 , and U19 AI135972 ) and by funding from F. Hoffmann-La Roche and Vir Biotechnology to N.J.K. and R01 AI147837 to O.I. A.M. holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund , is an investigator at the Chan Zuckerberg Biohub, and has received funding from the Innovative Genomics Institute (IGI) and the Parker Institute for Cancer Immunotherapy (PICI). P.B. is supported by the Helmut Horten Stiftung and the ETH Z{\"u}rich Foundation . A.M. is supported by a Cancer Research Institute (CRI) Lloyd J. Old STAR career award. Funding Information: This research was funded by grants from the National Institutes of Health (P50 AI150476, U19 AI135990, and U19 AI135972) and by funding from F. Hoffmann-La Roche and Vir Biotechnology to N.J.K. and R01 AI147837 to O.I. A.M. holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund, is an investigator at the Chan Zuckerberg Biohub, and has received funding from the Innovative Genomics Institute (IGI) and the Parker Institute for Cancer Immunotherapy (PICI). P.B. is supported by the Helmut Horten Stiftung and the ETH Z?rich Foundation. A.M. is supported by a Cancer Research Institute (CRI) Lloyd J. Old STAR career award. Conceptualization, J.R.J. and N.J.K.; methodology, J.R.J. D.C.C. J.F.H. D.L. and O.I.F.; investigation, J.R.J. D.C.C. J.F.H. J.M. J.S. R.H. T.L.J. B.W.N. D.L. O.I.F. A.P.K. and P.A.; software, J.R.J. E.V. and P.B.; formal analysis, J.R.J. and E.V.; writing ? original draft, J.R.J.; writing ? review & editing, J.R.J. and N.J.K.; visualization, J.R.J. and M.S.; supervision, J.R.J. A.M. A.D.F. J.A.T.Y. O.I.F. J.S.C. and N.J.K.; funding acquisition, J.R.J. A.D.F. J.S.C. J.A.Y. and N.J.K. The Krogan Laboratory has received research support from Vir Biotechnology and F. Hoffmann-La Roche. N.J.K. has consulting agreements with the Icahn School of Medicine at Mount Sinai, Maze Therapeutics, and Interline Therapeutics, is a shareholder in Tenaya Therapeutics, Maze Therapeutics, and Interline Therapeutics, and is a financially compensated scientific advisory board member for GEn1E Lifesciences, Inc. A.M. is a compensated cofounder, a member of the board of directors, and a member of the scientific advisory boards of Spotlight Therapeutics and Arsenal Biosciences. A.M. is a cofounder, a member of the board of directors, and a member of the scientific advisory board of Survey Genomics. A.M. is a compensated member of the scientific advisory board of NewLimit. A.M. owns stock in Arsenal Biosciences, Spotlight Therapeutics, NewLimit, Survey Genomics, PACT Pharma, and Merck. A.M. has received fees from 23andMe, PACT Pharma, Juno Therapeutics, Trizell, Vertex, Merck, Amgen, Genentech, AlphaSights, Rupert Case Management, Bernstein, and ALDA. A.M. is an investor in and informal advisor to Offline Ventures and a client of EPIQ. The Marson lab has received research support from Juno Therapeutics, Epinomics, Sanofi, GlaxoSmithKline, Gilead, and Anthem. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = apr,
day = "12",
doi = "10.1016/j.celrep.2022.110690",
language = "English",
volume = "39",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "2",
}