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Cell DOI:10.1016/j.cell.2009.12.018

A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection.

Publication TypeJournal Article
Year of Publication2009
AuthorsShapira, SD, Gat-Viks, I, Shum, BOV, Dricot, A, de Grace, MM, Wu, L, Gupta, PB, Hao, T, Silver, SJ, Root, DE, Hill, DE, Regev, A, Hacohen, N
Date Published2009 Dec 24
KeywordsApoptosis, Epithelial Cells, Gene Expression Profiling, Host-Pathogen Interactions, Humans, Influenza A Virus, H1N1 Subtype, Interferons, Lung, Proteomics, RNA, Small Interfering, RNA, Viral, Two-Hybrid System Techniques, Viral Nonstructural Proteins, Viral Proteins, Wnt Proteins

During the course of a viral infection, viral proteins interact with an array of host proteins and pathways. Here, we present a systematic strategy to elucidate the dynamic interactions between H1N1 influenza and its human host. A combination of yeast two-hybrid analysis and genome-wide expression profiling implicated hundreds of human factors in mediating viral-host interactions. These factors were then examined functionally through depletion analyses in primary lung cells. The resulting data point to potential roles for some unanticipated host and viral proteins in viral infection and the host response, including a network of RNA-binding proteins, components of WNT signaling, and viral polymerase subunits. This multilayered approach provides a comprehensive and unbiased physical and regulatory model of influenza-host interactions and demonstrates a general strategy for uncovering complex host-pathogen relationships.


Alternate JournalCell
PubMed ID20064372
PubMed Central IDPMC2892837
Grant ListDP2 OD002230-01 / OD / NIH HHS / United States
U54 AI057159 / AI / NIAID NIH HHS / United States
R01 HG001715 / HG / NHGRI NIH HHS / United States
P50 HG004233 / HG / NHGRI NIH HHS / United States
DP2 OD002230 / OD / NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
U01 AI074575 / AI / NIAID NIH HHS / United States
U01 AI074575-01 / AI / NIAID NIH HHS / United States
DP1 OD003958 / OD / NIH HHS / United States