Article ; Online: Inducible nitric oxide contributes to viral pathogenesis following highly pathogenic influenza virus infection in mice.
The Journal of infectious diseases
2013 Volume 207, Issue 10, Page(s) 1576–1584
Abstract: ... a potent signaling molecule in inflammation, was evaluated following highly pathogenic influenza virus ... Highly pathogenic influenza A viruses, including avian H5N1 viruses and the 1918 pandemic virus ... to a seasonal H1N1 virus. Mice deficient in inducible NO synthase (NOS2(-/-)) exhibited reduced morbidity ...
| Abstract | Highly pathogenic influenza A viruses, including avian H5N1 viruses and the 1918 pandemic virus, cause severe respiratory disease in humans and animals. Virus infection is followed by intense pulmonary congestion due to an extensive influx of macrophages and neutrophils, which can release large quantities of reactive oxygen species potentially contributing to the pathogenesis of lung disease. Here, the role of nitric oxide (NO), a potent signaling molecule in inflammation, was evaluated following highly pathogenic influenza virus challenge in mice. We observed higher levels of NO in mice infected with H5N1 and 1918 viruses as compared to a seasonal H1N1 virus. Mice deficient in inducible NO synthase (NOS2(-/-)) exhibited reduced morbidity, reduced mortality, and diminished cytokine production in lung tissue following H5N1 and 1918-virus challenge, compared with wild-type control mice. Furthermore, systemic treatment of mice with the NOS inhibitor NG-monomethyl-l-arginine delayed weight loss and death among 1918 virus infected mice compared to untreated control animals. This study demonstrates that NO contributes to the pathogenic outcome of H5N1 and 1918 viral infections in the mouse model. |
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| MeSH term(s) | Animals ; Chemokines/blood ; Cytokines/blood ; Disease Models, Animal ; Female ; Influenza A Virus, H1N1 Subtype/pathogenicity ; Influenza A Virus, H5N1 Subtype/pathogenicity ; Lung/pathology ; Lung/virology ; Macrophages/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Neutrophils/cytology ; Neutrophils/immunology ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type II/genetics ; Nitric Oxide Synthase Type II/metabolism ; Orthomyxoviridae Infections/pathology ; Orthomyxoviridae Infections/virology ; Pandemics ; omega-N-Methylarginine/pharmacology | ||||||||||
| Chemical Substances | Chemokines ; Cytokines ; omega-N-Methylarginine (27JT06E6GR) ; Nitric Oxide (31C4KY9ESH) ; Nitric Oxide Synthase Type II (EC 1.14.13.39) ; Nos2 protein, mouse (EC 1.14.13.39) | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2013-05-15 | ||||||||||
| Publishing country | United States | ||||||||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S. | ||||||||||
| ZDB-ID | 3019-3 | ||||||||||
| ISSN | 1537-6613 ; 0022-1899 | ||||||||||
| ISSN (online) | 1537-6613 | ||||||||||
| ISSN | 0022-1899 | ||||||||||
| DOI | 10.1093/infdis/jit062 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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