title: Strain-specific contribution of NS1-activated phosphoinositide 3-kinase signaling to influenza A virus replication and virulence.
abstract: 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.
authors.affiliation: Department of Microbiology, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Ayllon
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Hale
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
mesh_terms: D000818:Animals; D002460:Cell Line; D004285:Dogs; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000378:metabolism / Q000401:mortality / Q000821:virology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction; D016019:Survival Analysis; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014774:Virulence; D014779:Virus Replication
chemical_list: C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins; D019869:Phosphatidylinositol 3-Kinases