Host-specific SRSF7 regulates polymerase activity and replication of influenza A virus.

Abstract

Avian influenza viruses crossing the host barrier to infect humans have caused great panic in human society and seriously threatened public health. Herein, we revealed that knockdown of SRSF7 significantly down-regulated influenza virus titers and viral protein expression. We further observed for the first time that human SRSF7, but not avian SRSF7, significantly inhibited polymerase activity (PB2₆₂₇E). Molecular mapping demonstrated that amino acids 206 to 228 of human SRSF7 play a decisive role in regulating the polymerase activity, which contains the amino acid motif absent in avian SRSF7. Importantly, our results illustrated that the PB2₆₂₇K-encoding influenza virus induces SRSF7 protein degradation more strongly via the lysosome pathway and not via the proteasome pathway. Functional enrichment analysis of SRSF7-related KEGG pathways indicated that SRSF7 is closely related to cell growth and death. Lastly, our results showed that knocking down SRSF7 interferes with normal polymerase activity. Taken together, our results advance our understanding of interspecies transmission and our findings point out new targets for the development of drugs preventing or treating influenza virus infection.