2026-09-07T22:44:58Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/95252024-09-05T00:05:22Zcom_10259_4862com_10259_5086com_10259_2604col_10259_4863

Ayllón Barasoain, Juan 852 600 0000-0002-7556-8106 Hale, Benjamin G. acc3bd63-b78d-4900-a8fb-06b2d01623cf 600 García Sastre, Adolfo 9de2ea8b-c019-414d-bb90-b1d51ef5bbd7 600 2024-09-04T07:54:51Z 2024-09-04T07:54:51Z 2012-05 0022-538X http://hdl.handle.net/10259/9525 10.1128/jvi.06722-11 1098-5514 We generated influenza A viruses expressing mutant NS1 proteins unable to activate phosphoinositide 3-kinase (PI3K) in two mouse-lethal strains. The recombinant A/Puerto Rico/8/34 (rPR8) mutant virus strain was attenuated and caused reduced morbidity/mortality. For the recombinant A/WSN/33 (rWSN) virus strain, the inability to stimulate PI3K had minimal impact on replication or morbidity/mortality. Cell-based assays revealed subtly distinct intracellular sites of NS1 localization and PI3K activation between the strains. We hypothesize that specific spatially regulated NS1-activated PI3K signaling, rather than simply the total level of active PI3K, is important for virus replication and virulence. This work was supported by NIH funding to A.G.-S. (Center for Research on Influenza Pathogenesis [CRIP], NIAID CEIRS contract HHSN266200700010C, and NIAID grant RO1AI046954). Confocal laser scanning microscopy was performed at the MSSM-Microscopy Shared Resource Facility, which is supported with funding from a National Institutes of Health-National Cancer Institute (NIH-NCI) shared resources grant (5R24 CA095823-04), an NSF Major Research Instrumentation grant (DBI-9724504), and an NIH shared instrumentation grant (1 S10 RR0 9145-01). application/pdf eng American Society for Microbiology Journal of Virology. 2012, V. 86, n. 9, p. 5366–5370 https://doi.org/10.1128/jvi.06722-11 info:eu-repo/grantAgreement/NIAID//HHSN266200700010C/US/ info:eu-repo/grantAgreement/NIAID//RO1AI046954/US/ info:eu-repo/grantAgreement/NCI//5R24 CA095823-04/US/ info:eu-repo/grantAgreement/NSF//DBI-9724504/US/ info:eu-repo/grantAgreement/NIH//1 S10 RR0 9145-01/US/ Medicina Salud Microbiología Enfermedades infecciosas Medicine Health Microbiology Communicable diseases Strain-Specific Contribution of NS1-Activated Phosphoinositide 3-Kinase Signaling to Influenza A Virus Replication and Virulence info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/openAccess Journal of Virology 86 9 5366 5370 THUMBNAIL Ayllon-jv_2012.pdf.jpg Ayllon-jv_2012.pdf.jpg IM Thumbnail image/jpeg 3442 https://riubu.ubu.es/bitstream/10259/9525/3/Ayllon-jv_2012.pdf.jpg 3aaf376a4fb7d890b94adb8281ee14c0 MD5 3 LICENSE license.txt license.txt text/plain; charset=utf-8 999 https://riubu.ubu.es/bitstream/10259/9525/2/license.txt b295bcbce42e2caabeb0c623d3860c06 MD5 2 ORIGINAL Ayllon-jv_2012.pdf Ayllon-jv_2012.pdf application/pdf 1470343 https://riubu.ubu.es/bitstream/10259/9525/1/Ayllon-jv_2012.pdf 0565ea4365cb84690fe123d652c89d6a MD5 1 10259/9525 oai:riubu.ubu.es:10259/9525 2024-09-05 02:05:22.889 Repositorio Institucional de la Universidad de Burgos bubrep@ubu.es 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