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Abstract
In the present study, we demonstrate the effect of individual and mixtures of shRNAs
targeting the NS gene to treat an established infection of influenza A virus (IAV).
We prepared 10 shRNAs targeting the NS gene of the IAV, and these shRNAs were tested
individually or in mixtures 16h after infection. Our results revealed: (i) shRNA targeting
the NS1 transcript decreased the virus titre up to 21% (P<0.01), (ii) shRNA targeting
NEP transcript did not influence the replication of IAV in the infected cells; (iii)
a mixture of shRNAs targeting the NS1 transcript was less effective than the individual
shRNAs and decreased the virus titre up to 42% in vitro; (iv) a mixture of individually
inactive shRNAs targeting the NEP transcript significantly inhibited the replication
of IAV in vitro; (v) the activities of the individual shRNAs in vivo predominantly
corresponded to their activities in vitro; (vi) a synergistic effect of the shRNAs
was observed in vivo; and (vii) a shRNA targeting the region common to both the NS1
and NEP transcripts, shNS593, exhibited the strongest inhibition and reduced the virus
titre up to 16.4% in vitro, prolonged the survival of the mice by three days and abolished
the protective effect of other shRNAs in vivo. shRNAs inhibited influenza virus infection
in a gene-specific manner. NS1 mRNA was significantly reduced in lungs treated with
shRNAs and the levels of RIG-1, IFN-α, IFN-β and IFN-γ mRNAs shRNAs were not altered.