Host lncRNA assists the nuclear import of influenza A virus protein PB2 in a species-specific manner

Long noncoding RNAs (lncRNAs) have been reported to modulate immune responses to viral infections. However, it remains largely unexplored how viruses exploit host lncRNAs to promote viral replication. Here, we found that an lncRNA, called lnc-ALOX12, is upregulated specifically in cells infected by influenza A virus (IAV). Lnc-ALOX12 promotes IAV infection through associating with IAV RNA polymerase subunit PB2, sustaining the interaction between PB2 and importin-α/β, thus warranting PB2 nuclear import and efficient viral RNA synthesis. Importantly, avian influenza A virus needs to mutate its PB2 protein in order to hijack human lnc-ALOX12 for efficient viral RNA synthesis in mammal cells. Therefore, our data support the dependence of IAV replication on host lncRNAs. This dependence is species-specific and acts as a barrier to cross-species transmission of avian influenza viruses.