title: Human-like PB2 627K influenza virus polymerase activity is regulated by importin-α1 and -α7.
abstract: Influenza A viruses may cross species barriers and transmit to humans with the potential to cause pandemics. Interplay of human- (PB2 627K) and avian-like (PB2 627E) influenza polymerase complexes with unknown host factors have been postulated to play a key role in interspecies transmission. Here, we have identified human importin-α isoforms (α1 and α7) as positive regulators of human- but not avian-like polymerase activity. Human-like polymerase activity correlated with efficient recruitment of α1 and α7 to viral ribonucleoprotein complexes (vRNPs) without affecting subcellular localization. We also observed that human-like influenza virus growth was impaired in α1 and α7 downregulated human lung cells. Mice lacking α7 were less susceptible to human- but not avian-like influenza virus infection. Thus, α1 and α7 are positive regulators of human-like polymerase activity and pathogenicity beyond their role in nuclear transport.
authors.affiliation: Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Ben
authors.initials: B
authors.lastname: Hudjetz
authors.forename: Gülsah
authors.initials: G
authors.lastname: Gabriel
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002461:Cell Line, Transformed; D015536:Down-Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity; D007251:Influenza, Human / Q000635:transmission* / Q000821:virology; D008168:Lung / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000635:transmission* / Q000821:virology; D011485:Protein Binding; D020033:Protein Isoforms; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism*
chemical_list: C502893:PB2 protein, influenza virus; D020033:Protein Isoforms; D014764:Viral Proteins; D028901:alpha Karyopherins