Time-resolved global and chromatin proteomics during herpes simplex virus type 1 (HSV-1) infection

Katarzyna Kulej, Daphne C. Avgousti, Simone Sidoli, Christin Herrmann, Ashley N. Della Fera, Eui Tae Kim, Benjamin A. Garcia, Matthew D. Weitzman

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Herpes simplex virus (HSV-1) lytic infection results in global changes to the host cell proteome and the proteins associated with host chromatin. We present a system level characterization of proteome dynamics during infection by performing a multi-dimensional analysis during HSV-1 lytic infection of human foreskin fibroblast (HFF) cells. Our study includes identification and quantification of the host and viral proteomes, phosphoproteomes, chromatin bound proteomes and post-translational modifications (PTMs) on cellular histones during infection. We analyzed proteomes across six time points of virus infection (0, 3, 6, 9, 12 and 15 h post-infection) and clustered trends in abundance using fuzzy c-means. Globally, we accurately quantified more than 4000 proteins, 200 differently modified histone peptides and 9000 phosphorylation sites on cellular proteins. In addition, we identified 67 viral proteins and quantified 571 phosphorylation events (465 with high confidence site localization) on viral proteins, which is currently the most comprehensive map of HSV-1 phosphoproteome. We investigated chromatin bound proteins by proteomic analysis of the high-salt chromatin fraction and identified 510 proteins that were significantly different in abundance during infection. We found 53 histone marks significantly regulated during virus infection, including a steady increase of histone H3 acetylation (H3K9ac and H3K14ac). Our data provide a resource of unprecedented depth for human and viral proteome dynamics during infection. Collectively, our results indicate that the proteome composition of the chromatin of HFF cells is highly affected during HSV-1 infection, and that phosphorylation events are abundant on viral proteins. We propose that our epi-proteomics approach will prove to be important in the characterization of other model infectious systems that involve changes to chromatin composition.

Original languageEnglish (US)
Pages (from-to)S92-S107
JournalMolecular and Cellular Proteomics
Volume16
Issue number4
DOIs
StatePublished - Apr 2017

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

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    Kulej, K., Avgousti, D. C., Sidoli, S., Herrmann, C., Della Fera, A. N., Kim, E. T., Garcia, B. A., & Weitzman, M. D. (2017). Time-resolved global and chromatin proteomics during herpes simplex virus type 1 (HSV-1) infection. Molecular and Cellular Proteomics, 16(4), S92-S107. https://doi.org/10.1074/mcp.M116.065987