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

First Author  Hudjetz B Year  2012
Journal  PLoS Pathog Volume  8
Issue  1 Pages  e1002488
PubMed ID  22275867 Mgi Jnum  J:195405
Mgi Id  MGI:5478713 Doi  10.1371/journal.ppat.1002488
Citation  Hudjetz B, et al. (2012) Human-like PB2 627K influenza virus polymerase activity is regulated by importin-alpha1 and -alpha7. PLoS Pathog 8(1):e1002488
abstractText  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-alpha isoforms (alpha1 and alpha7) as positive regulators of human- but not avian-like polymerase activity. Human-like polymerase activity correlated with efficient recruitment of alpha1 and alpha7 to viral ribonucleoprotein complexes (vRNPs) without affecting subcellular localization. We also observed that human-like influenza virus growth was impaired in alpha1 and alpha7 downregulated human lung cells. Mice lacking alpha7 were less susceptible to human- but not avian-like influenza virus infection. Thus, alpha1 and alpha7 are positive regulators of human-like polymerase activity and pathogenicity beyond their role in nuclear transport.
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