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 Young; Nevan J Krogan

doi:10.1016/j.celrep.2022.110690

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

Cell Rep. 2022 Apr 12;39(2):110690. doi: 10.1016/j.celrep.2022.110690.

Authors

Jeffrey R Johnson¹, David C Crosby², Judd F Hultquist³, Andrew P Kurland⁴, Prithy Adhikary⁴, Donna Li⁵, John Marlett⁶, Justine Swann⁶, Ruth Hüttenhain³, Erik Verschueren³, Tasha L Johnson³, Billy W Newton³, Michael Shales³, Viviana A Simon⁴, Pedro Beltrao⁷, Alan D Frankel², Alexander Marson⁸, Jeffery S Cox⁹, Oliver I Fregoso⁵, John A T Young¹⁰, Nevan J Krogan¹¹

Affiliations

¹ Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA 94158, USA; Gladstone Institute for Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA 94158, USA. Electronic address: jeffrey.johnson@mssm.edu.
² Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158, USA.
³ Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA 94158, USA; Gladstone Institute for Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA 94158, USA.
⁴ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁵ Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA.
⁶ Viral Vector Core, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
⁷ European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CD10 1SD, UK.
⁸ Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California San Francisco, San Francisco, CA 94143, USA; Innovative Genomics Institute, University of California Berkeley, Berkeley, CA 94720, USA; Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.
⁹ Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA.
¹⁰ Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
¹¹ Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA 94158, USA; Gladstone Institute for Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA 94158, USA. Electronic address: nevan.krogan@ucsf.edu.

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.

Publication types

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

MeSH terms

HIV Infections*
HIV Seropositivity*
HIV-1* / genetics
Humans
Protein Processing, Post-Translational
Proteomics
Ubiquitination

Abstract

Publication types

MeSH terms

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