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. |