RT info:eu-repo/semantics/article
T1 Influenza A virus NS1 protein mimics oncogenic PI3K resulting in isoform specific cellular redistribution and activation
A1 Aslam, Sadaf
A1 Sánchez-Aparicio, M. T.
A1 Siempelkamp, Braden D.
A1 Dornan, Gillian L.
A1 Tsolakos, Nikos
A1 Burke, John E.
A1 Hale, Benjamin G.
A1 García Sastre, Adolfo
A1 Ayllón Barasoain, Juan
K1 Influenza
K1 Oncogenesis
K1 PI3K
K1 Proteínas
K1 Proteins
AB The nonstructural protein 1 (NS1) of influenza A virus performs a broad variety ofproviral activities in the infected cell, primarily mediating evasion from the host innateimmune response by being the main viral interferon antagonist. However, there areseveral interactions whose biological relevance remains obscure, such as the ability ofNS1 to bind and activate class IA phosphoinositide 3-kinases(PI3Ks). PI3Ks are highlyregulated lipid kinases that act as critical nodes in multiple cell signaling networks andare also important proto-oncogenes.This activation is mediated by NS1 binding specificallyto the p85β subunit. To better understand the consequences of this interaction, wedeveloped a bimolecular fluorescence complementation (BiFC) assay to selectively trackthe different PI3K heterodimers and, using this system, we found that NS1 induces anisoform-specificrelocation and activation of the different PI3K heterodimers. We foundthat clinically relevant oncogenic mutations in both catalytic and regulatory subunits ofPI3K could mimic the effect caused by NS1, and partially rescue the loss of viral fitnessin a recombinant virus encoding a p85β-bindingdeficient NS1.
PB National Academy of Sciences
SN 1091-6490
YR 2025
FD 2025-08
LK https://hdl.handle.net/10259/10923
UL https://hdl.handle.net/10259/10923
LA eng
NO We thank Richard Cadagan, Elena Moreno, and Sara El Zahed for technical assistance. Confocal laser scanning microscopy was performed at the Icahn School of Medicine Microscopy Shared Resource facility. This work was partly supported by CRIPT (Center for Research on Influenza Pathogenesis and Transmission), a NIAID funded Center of Excellence for Influenza Research and Response (CEIRR, contract #75N93021C00014) to A.G.- S. The work was also partially supported by the Swiss NSF (Grant 31003A_159993 to B.G.H.) and the Cancer Research Society (CRS-  CRS- 1052949 to J.E.B.).
DS Repositorio Institucional de la Universidad de Burgos
RD 29-abr-2026