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

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 en...

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Published in:Cell reports (Cambridge) 2022-04, Vol.39 (2), p.110690-110690, Article 110690
Main Authors: Johnson, Jeffrey R., Crosby, David C., Hultquist, Judd F., Kurland, Andrew P., Adhikary, Prithy, Li, Donna, Marlett, John, Swann, Justine, Hüttenhain, Ruth, Verschueren, Erik, Johnson, Tasha L., Newton, Billy W., Shales, Michael, Simon, Viviana A., Beltrao, Pedro, Frankel, Alan D., Marson, Alexander, Cox, Jeffery S., Fregoso, Oliver I., Young, John A.T., Krogan, Nevan J.
Format: Article
Language:English
Subjects:
b56
histone h1
HIV Infections
HIV Seropositivity
HIV-1
HIV-1 - genetics
Humans
phosphorylation
pp2a
Protein Processing, Post-Translational
Proteomics
systems biology
Ubiquitination
vif
vpr
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Summary: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. [Display omitted] •Integrated analysis of HIV-1-mediated changes in post-translational modifications•HIV-1 requires Aurora kinase activity for productive infection•HIV-1 Vpr is associated with decreased ubiquitination of histone H1 isoforms Johnson et al. describe a quantitative resource of ubiquitination, phosphorylation, and protein abundance changes in cells infected with HIV-1. These data uncover a requirement for Aurora kinase activity in HIV-1 infection and find that the HIV-1 Vpr protein is associated with decreased histone H1 ubiquitination.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2022.110690