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

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-...

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Autores principales: Kong, Xiaoyuan, Zhang, Weidong, Lockey, Richard F, Auais, Alexander, Piedimonte, Giovanni, Mohapatra, Shyam S
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1805440/
https://www.ncbi.nlm.nih.gov/pubmed/17270047
http://dx.doi.org/10.1186/1479-0556-5-4
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author Kong, Xiaoyuan
Zhang, Weidong
Lockey, Richard F
Auais, Alexander
Piedimonte, Giovanni
Mohapatra, Shyam S
author_facet Kong, Xiaoyuan
Zhang, Weidong
Lockey, Richard F
Auais, Alexander
Piedimonte, Giovanni
Mohapatra, Shyam S
author_sort Kong, Xiaoyuan
collection PubMed
description 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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spelling pubmed-18054402007-02-27 Respiratory syncytial virus infection in Fischer 344 rats is attenuated by short interfering RNA against the RSV-NS1 gene Kong, Xiaoyuan Zhang, Weidong Lockey, Richard F Auais, Alexander Piedimonte, Giovanni Mohapatra, Shyam S Genet Vaccines Ther Research 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. BioMed Central 2007-02-01 /pmc/articles/PMC1805440/ /pubmed/17270047 http://dx.doi.org/10.1186/1479-0556-5-4 Text en Copyright © 2007 Kong et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Kong, Xiaoyuan
Zhang, Weidong
Lockey, Richard F
Auais, Alexander
Piedimonte, Giovanni
Mohapatra, Shyam S
Respiratory syncytial virus infection in Fischer 344 rats is attenuated by short interfering RNA against the RSV-NS1 gene
title Respiratory syncytial virus infection in Fischer 344 rats is attenuated by short interfering RNA against the RSV-NS1 gene
title_full Respiratory syncytial virus infection in Fischer 344 rats is attenuated by short interfering RNA against the RSV-NS1 gene
title_fullStr Respiratory syncytial virus infection in Fischer 344 rats is attenuated by short interfering RNA against the RSV-NS1 gene
title_full_unstemmed Respiratory syncytial virus infection in Fischer 344 rats is attenuated by short interfering RNA against the RSV-NS1 gene
title_short Respiratory syncytial virus infection in Fischer 344 rats is attenuated by short interfering RNA against the RSV-NS1 gene
title_sort respiratory syncytial virus infection in fischer 344 rats is attenuated by short interfering rna against the rsv-ns1 gene
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1805440/
https://www.ncbi.nlm.nih.gov/pubmed/17270047
http://dx.doi.org/10.1186/1479-0556-5-4
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