A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection.
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.
Shapira
Sagi D
SD
Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.
Gat-Viks
Irit
I
Shum
Bennett O V
BO
Dricot
Amelie
A
de Grace
Marciela M
MM
Wu
Liguo
L
Gupta
Piyush B
PB
Hao
Tong
T
Silver
Serena J
SJ
Root
David E
DE
Hill
David E
DE
Regev
Aviv
A
Hacohen
Nir
N
D017209:Apoptosis; D004847:Epithelial Cells / Q000821:virology; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity; D007372:Interferons / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000821:virology; D040901:Proteomics; D034741:RNA, Small Interfering / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism
C085820:INS1 protein, influenza virus; D034741:RNA, Small Interfering; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D051153:Wnt Proteins; D007372:Interferons