Influenza A virus NS1 protein activates the phosphatidylinositol 3-kinase (PI3K)/Akt pathway by direct interaction with the p85 subunit of PI3K.
Influenza A virus infection activates the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, but the mechanism is not clear. Here, it is reported that influenza A virus NS1 protein is responsible for PI3K/Akt pathway activation. It was demonstrated that the NS1 protein interacts with the p85 regulatory subunit of PI3K via direct binding to the SH3 and C-terminal SH2 domains of p85. Consensus binding motifs for SH3 and SH2 domains were found in influenza A virus NS1, namely an SH2-binding motif (YXXXM) at aa 89, SH3-binding motif 1 (PXXP) around aa 164 and SH3-binding motif 2 around aa 212. Mutant virus encoding NS1 protein with mutations in the SH-binding motifs failed to interact with SH domains of p85 and did not activate the PI3K/Akt pathway. The mutant virus is attenuated in Madin-Darby canine kidney cells. Our study has established a novel function of NS1: by interacting with p85 via the SH-binding motifs, NS1 can activate the PI3K/Akt pathway.
Shin
Yeun-Kyung
YK
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
Liu
Qiang
Q
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
Tikoo
Suresh K
SK
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
Babiuk
Lorne A
LA
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
Zhou
Yan
Y
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D029521:Alphainfluenzavirus / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D021122:Protein Subunits; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000494:pharmacology*
C085820:INS1 protein, influenza virus; D021122:Protein Subunits; D017361:Viral Nonstructural Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt