Human-like PB2 627K influenza virus polymerase activity is regulated by importin-α1 and -α7

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. © 2012 hudjetz,gabriel.