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Quantitative phosphoproteomics reveals extensive cellular reprogramming during HIV-1 entry.

Abstract
Receptor engagement by HIV-1 during host cell entry activates signaling pathways that can reprogram the cell for optimal viral replication. To obtain a global view of the signaling events induced during HIV-1 entry, we conducted a quantitative phosphoproteomics screen of primary human CD4(+) T cells after infection with an HIV-1 strain that engages the receptors CD4 and CXCR4. We quantified 1,757 phosphorylation sites with high stringency. The abundance of 239 phosphorylation sites from 175 genes, including several proteins in pathways known to be impacted by HIV-receptor binding, changed significantly within a minute after HIV-1 exposure. Several previously uncharacterized HIV-1 host factors were also identified and confirmed through RNAi depletion studies. Surprisingly, five serine/arginine-rich (SR) proteins involved in messenger RNA splicing, including the splicing factor SRm300 (SRRM2), were differentially phosophorylated. Mechanistic studies with SRRM2 suggest that HIV-1 modulates host cell alternative splicing machinery during entry in order to facilitate virus replication and release.
AuthorsJason A Wojcechowskyj, Chuka A Didigu, Jessica Y Lee, Nicholas F Parrish, Rohini Sinha, Beatrice H Hahn, Frederic D Bushman, Shane T Jensen, Steven H Seeholzer, Robert W Doms
JournalCell host & microbe (Cell Host Microbe) Vol. 13 Issue 5 Pg. 613-623 (May 15 2013) ISSN: 1934-6069 [Electronic] United States
PMID23684312 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier Inc. All rights reserved.
Chemical References
  • Phosphoproteins
  • Proteome
Topics
  • CD4-Positive T-Lymphocytes (virology)
  • Cells, Cultured
  • Gene Expression Regulation
  • HIV-1 (physiology)
  • Host-Pathogen Interactions
  • Humans
  • Phosphoproteins (analysis)
  • Proteome (analysis)
  • Proteomics (methods)
  • RNA Splicing
  • Virus Internalization
  • Virus Release
  • Virus Replication

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