Key result
Administration of siRNA targeted against the NS1 gene of influenza A virus resulted in a 92% reduction in NS1 gene expression in mice lungs and significantly reduced lung virus titers.
Why the study?
Does siRNA targeting the NS1 gene inhibit influenza A virus replication in MDCK cells and BALB/c mice?
Does siRNA targeting the NS1 gene inhibit influenza A virus replication in MDCK cells and BALB/c mice?
siRNA targeted against the NS1 gene of influenza A virus significantly reduces viral replication and gene expression in vitro and in vivo, suggesting potential as a nucleic acid-based antiviral therapy.
Hypothesis-generating for NS1 siRNA in influenza; leaves open translation to human therapy.
Nonstructural protein 1 (NS1) of influenza A viruses counteracts the host immune response against the influenza viruses by not only inhibiting the nuclear export and maturation of host cell messenger RNA (mRNA), but by also blocking the double-stranded RNA-activated protein kinase-mediated inhibition of viral RNA translation. Reduction of NS1 gene product in the host cell may be a potent antiviral strategy to provide protection against the influenza virus infection. We used small interfering RNAs (siRNAs) synthesized against the viral mRNA to down regulate the NS1 gene and observed its effect on inhibition of virus replication. When NS1 gene-specific siRNA were transfected in Madin Darby canine kidney (MDCK) cells followed by influenza A virus infection, approximately 60% inhibition in intracellular levels of NS1 RNA was observed. When siRNA was administered in BALB/c mice, 92% reduction in the levels of NS1 gene expression in mice lungs was observed. A significant reduction in the lung virus titers and cytokine levels was also detected in the presence of siRNAs as compared with the untreated control. The study was validated by the use of selectively disabled mutants of each set of siRNA. Our findings suggest that siRNA targeted against NS1 gene of influenza A virus can provide considerable protection to the virus-infected host cells and may be used as potential candidates for nucleic acid-based antiviral therapy for prevention of influenza A virus infection.
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Rajput et al. (2012) studied Influenza A virus infection. small interfering RNAs (siRNAs) targeted against NS1 gene vs. untreated control was evaluated on NS1 gene expression in mice lungs. Administration of siRNA targeted against the NS1 gene of influenza A virus resulted in a 92% reduction in NS1 gene expression in mice lungs and significantly reduced lung virus titers.
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