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

Strain-Specific Contribution of NS1-Activated Phosphoinositide 3-Kinase Signaling to Influenza A Virus Replication and Virulence Ayllón Barasoain, Juan Hale, Benjamin G. García Sastre, Adolfo Medicina Salud Microbiología Enfermedades infecciosas Medicine Health Microbiology Communicable diseases 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). 2024-09-04T07:54:51Z 2024-09-04T07:54:51Z 2012-05 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 0022-538X http://hdl.handle.net/10259/9525 10.1128/jvi.06722-11 1098-5514 eng 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/ info:eu-repo/semantics/openAccess application/pdf American Society for Microbiology https://riubu.ubu.es/bitstream/10259/9525/3/Ayllon-jv_2012.pdf.jpg Hispana TEXT http://rightsstatements.org/vocab/CNE/1.0/ RIUBU. Repositorio Institucional de la Universidad de Burgos http://hdl.handle.net/10259/9525