2026-04-28T21:00:05Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/109232025-10-04T00:05:28Zcom_10259_4862com_10259_5086com_10259_2604col_10259_4863

Aslam, Sadaf 34ce451c-1783-43a0-99fe-d911a3c31bcd 600 Sánchez-Aparicio, M. T. ea4cf178-af81-44b8-a090-cc7b002ed87e 600 Siempelkamp, Braden D. 06592ef2-8751-4f13-ab97-4b7ce500ab26 600 Dornan, Gillian L. 70604d2e-74c9-4fc0-a072-bb2fff098fc6 500 Tsolakos, Nikos 29044da5-5f62-46e7-beed-a5c3d09b74dd 500 Burke, John E. 85c80c5b-7235-4c21-b5b9-39c3b0d46402 500 Hale, Benjamin G. acc3bd63-b78d-4900-a8fb-06b2d01623cf 500 García Sastre, Adolfo 9de2ea8b-c019-414d-bb90-b1d51ef5bbd7 600 Ayllón Barasoain, Juan 852 500 0000-0002-7556-8106 2025-10-03T12:13:48Z 2025-10-03T12:13:48Z 2025-08 1091-6490 https://hdl.handle.net/10259/10923 10.1073/pnas.2423066122 The nonstructural protein 1 (NS1) of influenza A virus performs a broad variety of proviral activities in the infected cell, primarily mediating evasion from the host innate immune response by being the main viral interferon antagonist. However, there are several interactions whose biological relevance remains obscure, such as the ability of NS1 to bind and activate class IA phosphoinositide 3-kinases (PI3Ks). PI3Ks are highly regulated lipid kinases that act as critical nodes in multiple cell signaling networks and are also important proto-oncogenes. This activation is mediated by NS1 binding specifically to the p85β subunit. To better understand the consequences of this interaction, we developed a bimolecular fluorescence complementation (BiFC) assay to selectively track the different PI3K heterodimers and, using this system, we found that NS1 induces an isoform-specific relocation and activation of the different PI3K heterodimers. We found that clinically relevant oncogenic mutations in both catalytic and regulatory subunits of PI3K could mimic the effect caused by NS1, and partially rescue the loss of viral fitness in a recombinant virus encoding a p85β-binding deficient NS1. 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.). application/pdf eng National Academy of Sciences Proceedings of the National Academy of Sciences. 2025, V.122, n. 32, e2423066122 https://doi.org/10.1073/pnas.2423066122 Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Influenza Oncogenesis PI3K Proteínas Proteins Influenza A virus NS1 protein mimics oncogenic PI3K resulting in isoform specific cellular redistribution and activation info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Proceedings of the National Academy of Sciences of the United States of America 122 32 THUMBNAIL Aslam-pnas _2025.pdf.jpg Aslam-pnas _2025.pdf.jpg IM Thumbnail image/jpeg 5053 https://riubu.ubu.es/bitstream/10259/10923/4/Aslam-pnas%20_2025.pdf.jpg 378472861eb8de946c28ba9a8ff980cc MD5 4 LICENSE license.txt license.txt text/plain; charset=utf-8 999 https://riubu.ubu.es/bitstream/10259/10923/3/license.txt b295bcbce42e2caabeb0c623d3860c06 MD5 3 CC-LICENSE license_rdf license_rdf application/rdf+xml; charset=utf-8 805 https://riubu.ubu.es/bitstream/10259/10923/2/license_rdf 4460e5956bc1d1639be9ae6146a50347 MD5 2 ORIGINAL Aslam-pnas _2025.pdf Aslam-pnas _2025.pdf application/pdf 3833747 https://riubu.ubu.es/bitstream/10259/10923/1/Aslam-pnas%20_2025.pdf 227ef64ec9ecd86641111a94ba5f85aa MD5 1 10259/10923 oai:riubu.ubu.es:10259/10923 2025-10-04 02:05:28.205 Repositorio Institucional de la Universidad de Burgos bubrep@ubu.es RWwgYXV0b3IgY29tbyDDum5pY28gdGl0dWxhciBkZSBsb3MgZGVyZWNob3MgZGUgcHJvcGllZGFkIGludGVsZWN0dWFsIGRlIGxhIG9icmEsIG8gZGlzcG9uaWVuZG8gZGUgbG9zIGRlYmlkb3MgcGVybWlzb3MgZGUgbG9zIG90cm9zIHRpdHVsYXJlcywgc2kgbG9zIGh1YmllcmEsIHkgZW4gdmlydHVkIGRlIGxvcyBkZXJlY2hvcyBxdWUgbGUgY29uZmllcmUgbGEgbGVnaXNsYWNpw7NuIHZpZ2VudGUgc29icmUgcHJvcGllZGFkIGludGVsZWN0dWFsIHkgZGVyZWNob3MgZGUgYXV0b3IsIA0KQVVUT1JJWkEgYSBsYSBVbml2ZXJzaWRhZCBkZSBCdXJnb3MgYSBkaWZ1bmRpciwgZGUgbWFuZXJhIGdyYXR1aXRhLCBlbCBjb250ZW5pZG8gZGUgbG9zIGFyY2hpdm9zIGRpZ2l0YWxlcyBxdWUgY29ycmVzcG9uZGVuIGFsIGRvY3VtZW50byBkZXNjcml0byBhbnRlcmlvcm1lbnRlLCBjb24gY2Fyw6FjdGVyIG5vIGV4Y2x1c2l2byB5IGRlIG1hbmVyYSBww7pibGljYSBlbiBhY2Nlc28gYWJpZXJ0byBhIHRyYXbDqXMgZGUgSW50ZXJuZXQsIHBhcmEgbG8gcXVlIGxhIEJpYmxpb3RlY2EgcHJvY2VkZXLDoSBhIGFyY2hpdmFybG9zIGVuIGVsIFJlcG9zaXRvcmlvIEluc3RpdHVjaW9uYWwuIEFzaW1pc21vIGF1dG9yaXphIGEgbGEgVW5pdmVyc2lkYWQgZGUgQnVyZ29zIGEgcmVhbGl6YXIgbGFzIHRyYW5zZm9ybWFjaW9uZXMgbmVjZXNhcmlhcyBkZSBmb3JtYXRvLCBubyBkZSBjb250ZW5pZG8sIHBhcmEgZ2FyYW50aXphciBsYSBwcmVzZXJ2YWNpw7NuIHkgZWwgYWNjZXNvIGVuIGVsIGZ1dHVyby4NCg0KRWwgYXV0b3IgZGlzcG9uZSwgZW4gdG9kbyBjYXNvLCBkZWwgZGVyZWNobyBhIHJldm9jYXIgZXN0YSBhdXRvcml6YWNpw7NuLg0KDQpMYSBjZXNpw7NuIGRlIGRlcmVjaG9zIGRlIGVzdGEgb2JyYSBzZSBlbmN1ZW50cmEgc3VqZXRhIGEgbGEgbGVnaXNsYWNpw7NuIHZpZ2VudGUgc29icmUgcHJvcGllZGFkIGludGVsZWN0dWFsIHkgZGVyZWNob3MgZGUgYXV0b3Iu