Global post-translational modification profiling of HIV-1-infected cells reveals mechanisms of host cellular pathway
Jeffrey R Johnson1, David C Crosby2, Judd F Hultquist1
1Department 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.
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.
