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

Publication ,  Journal Article
Wojcechowskyj, JA; Didigu, CA; Lee, JY; Parrish, NF; Sinha, R; Hahn, BH; Bushman, FD; Jensen, ST; Seeholzer, SH; Doms, RW
Published in: Cell Host Microbe
May 15, 2013

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.

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Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

May 15, 2013

Volume

13

Issue

5

Start / End Page

613 / 623

Location

United States

Related Subject Headings

  • Virus Replication
  • Virus Release
  • Virus Internalization
  • RNA Splicing
  • Proteomics
  • Proteome
  • Phosphoproteins
  • Immunology
  • Humans
  • Host-Pathogen Interactions
 

Citation

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Wojcechowskyj, J. A., Didigu, C. A., Lee, J. Y., Parrish, N. F., Sinha, R., Hahn, B. H., … Doms, R. W. (2013). Quantitative phosphoproteomics reveals extensive cellular reprogramming during HIV-1 entry. Cell Host Microbe, 13(5), 613–623. https://doi.org/10.1016/j.chom.2013.04.011
Wojcechowskyj, Jason A., Chuka A. Didigu, Jessica Y. Lee, Nicholas F. Parrish, Rohini Sinha, Beatrice H. Hahn, Frederic D. Bushman, Shane T. Jensen, Steven H. Seeholzer, and Robert W. Doms. “Quantitative phosphoproteomics reveals extensive cellular reprogramming during HIV-1 entry.Cell Host Microbe 13, no. 5 (May 15, 2013): 613–23. https://doi.org/10.1016/j.chom.2013.04.011.
Wojcechowskyj JA, Didigu CA, Lee JY, Parrish NF, Sinha R, Hahn BH, et al. Quantitative phosphoproteomics reveals extensive cellular reprogramming during HIV-1 entry. Cell Host Microbe. 2013 May 15;13(5):613–23.
Wojcechowskyj, Jason A., et al. “Quantitative phosphoproteomics reveals extensive cellular reprogramming during HIV-1 entry.Cell Host Microbe, vol. 13, no. 5, May 2013, pp. 613–23. Pubmed, doi:10.1016/j.chom.2013.04.011.
Wojcechowskyj JA, Didigu CA, Lee JY, Parrish NF, Sinha R, Hahn BH, Bushman FD, Jensen ST, Seeholzer SH, Doms RW. Quantitative phosphoproteomics reveals extensive cellular reprogramming during HIV-1 entry. Cell Host Microbe. 2013 May 15;13(5):613–623.
Journal cover image

Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

May 15, 2013

Volume

13

Issue

5

Start / End Page

613 / 623

Location

United States

Related Subject Headings

  • Virus Replication
  • Virus Release
  • Virus Internalization
  • RNA Splicing
  • Proteomics
  • Proteome
  • Phosphoproteins
  • Immunology
  • Humans
  • Host-Pathogen Interactions