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Respiratory syncytial virus infection in Fischer 344 rats is attenuated by short interfering RNA against the RSV-NS1 gene

Author(s): Kong Xiaoyuan | Zhang Weidong | Lockey Richard | Auais Alexander | Piedimonte Giovanni | Mohapatra Shyam

Journal: Genetic Vaccines and Therapy
ISSN 1479-0556

Volume: 5;
Issue: 1;
Start page: 4;
Date: 2007;
Original page

Abstract Background Respiratory syncytial virus (RSV) causes severe bronchiolitis and is a risk factor for asthma. Since there is no commercially available vaccine against RSV, a short interfering RNA against the RSV-NS1gene (siNS1) was developed and its potential for decreasing RSV infection and infection-associated inflammation in rats was tested. Methods Plasmids encoding siNS1 or an unrelated siRNA were complexed with a chitosan nanoparticle delivery agent and administered intranasally. Control animals received a plasmid for a non-specific siRNA. After expression of the plasmid in lung cells for 24 hours, the rats were intranasally infected with RSV. Results Prophylaxis with siNS1 significantly reduced lung RSV titers and airway hyperreactivity to methacholine challenge compared to the control group. Lung sections from siNS1-treated rats showed a sizable reduction in goblet cell hyperplasia and in lung infiltration by inflammatory cells, both characteristics of asthma. Also, bronchoalveolar lavage samples from siNS1-treated animals had fewer eosinophils. Treatment of rats with siNS1 prior to RSV exposure was effective in reducing virus titers in the lung and in preventing the inflammation and airway hyperresponsiveness associated with the infection that has been linked to development of asthma. Conclusion The use of siNS1 prophylaxis may be an effective method for preventing RSV bronchiolitis and potentially reducing the later development of asthma associated with severe respiratory infections.
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