Short-hairpin RNAs delivered by recombinant adeno-associated virus inhibited the replication of influenza A viruses in vitro

Antiviral short-hairpin RNAs (shRNAs) delivered by recombinant adeno-associated virus (rAAV) were investigated for their potential prophylactic and therapeutic applications related to the influenza A virus (IAV). To express shRNAs efficiently, an H1 promoter was inserted into the commercial rAAV2 system. The modified rAAV2 system could express shRNAs, and the purified rAAV was obtained at levels over 10(13) viral genomes/ml and 10(10) viral infection units/ml. The shNP-1496-n and shM2-925 delivered by rAAV could inhibit the replication of the H1N1 and H5N1 virus by targeting the conserved regions of the IAV nucleoprotein and matrix 2 genes in MDCK cells. The shNP-1496-n and shM2-925 expressed by rAAV could provide potent and long-term anti-H5N1 virus effects in rAAV-shRNA-enriched MDCK cells. Our findings provide a rational basis for developing RNA interference for the prevention and therapy of IAV infection.

Automated summary

In this study, antiviral shRNAs were delivered via rAAV to efficiently inhibit the replication of H1N1 and H5N1 viruses, providing a rational basis for developing RNA interference for the prevention and therapy of IAV infection.