Human-like PB2 627K Influenza Virus Polymerase Activity Is Regulated by Importin-α1 and -α7

PLoS Pathogens

Ben Hudjetz¹  Gülsah Gabriel¹ 

[1] Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany

关键词: Polymerases;    293T cells;    Influenza viruses;    Small interfering RNAs;    Cell binding;    Pathogenesis;    Cargo proteins;    Transfection;   

DOI  :  10.1371/journal.ppat.1002488

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY