| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3352851 | Immunity | 2016 | 13 Pages |
•Generated replication-competent, tagged influenza viruses•Constructed human-influenza interactome network during an infection•Mathematical modeling revealed host targets for pan-viral inhibition•Sec61 inhibition alters viral proteostasis and suppresses viral replication
SummaryViruses are obligate parasites and thus require the machinery of the host cell to replicate. Inhibition of host factors co-opted during active infection is a strategy hosts use to suppress viral replication and a potential pan-antiviral therapy. To define the cellular proteins and processes required for a virus during infection is thus crucial to understanding the mechanisms of virally induced disease. In this report, we generated fully infectious tagged influenza viruses and used infection-based proteomics to identify pivotal arms of cellular signaling required for influenza virus growth and infectivity. Using mathematical modeling and genetic and pharmacologic approaches, we revealed that modulation of Sec61-mediated cotranslational translocation selectively impaired glycoprotein proteostasis of influenza as well as HIV and dengue viruses and led to inhibition of viral growth and infectivity. Thus, by studying virus-human protein-protein interactions in the context of active replication, we have identified targetable host factors for broad-spectrum antiviral therapies.
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