Quantitative temporal viromics: An approach to investigate host-pathogen interaction

Michael P. Weekes*, Peter Tomasec, Edward L. Huttlin, Ceri A. Fielding, David Nusinow, Richard J. Stanton, Eddie C.Y. Wang, Rebecca Aicheler, Isa Murrell, Gavin W.G. Wilkinson, Paul J. Lehner, Steven P. Gygi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

331 Citations (Scopus)

Abstract

A systematic quantitative analysis of temporal changes in host and viral proteins throughout the course of a productive infection could provide dynamic insights into virus-host interaction. We developed a proteomic technique called "quantitative temporal viromics" (QTV), which employs multiplexed tandem-mass-tag-based mass spectrometry. Human cytomegalovirus (HCMV) is not only an important pathogen but a paradigm of viral immune evasion. QTV detailed how HCMV orchestrates the expression of >8,000 cellular proteins, including 1,200 cell-surface proteins to manipulate signaling pathways and counterintrinsic, innate, and adaptive immune defenses. QTV predicted natural killer and T cell ligands, as well as 29 viral proteins present at the cell surface, potential therapeutic targets. Temporal profiles of >80% of HCMV canonical genes and 14 noncanonical HCMV open reading frames were defined. QTV is a powerful method that can yield important insights into viral infection and is applicable to any virus with a robust in vitro model. PaperClip

Original languageEnglish
Pages (from-to)1460-1472
Number of pages13
JournalCell
Volume157
Issue number6
DOIs
Publication statusPublished - 5 Jun 2014
Externally publishedYes

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