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Article: Avian Influenza A H7N9 Virus Induces Severe Pneumonia in Mice without Prior Adaptation and Responds to a Combination of Zanamivir and COX-2 Inhibitor

TitleAvian Influenza A H7N9 Virus Induces Severe Pneumonia in Mice without Prior Adaptation and Responds to a Combination of Zanamivir and COX-2 Inhibitor
Authors
Issue Date2014
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
PLoS One, 2014, v. 9 n. 9, article no. e107966 How to Cite?
AbstractBackground Human infection caused by the avian influenza A H7N9 virus has a case-fatality rate of over 30%. Systematic study of the pathogenesis of avian H7N9 isolate and effective therapeutic strategies are needed. Methods BALB/c mice were inoculated intranasally with an H7N9 virus isolated from a chicken in a wet market epidemiologically linked to a fatal human case, (A/chicken/Zhejiang/DTID-ZJU01/2013 [CK1]), and with an H7N9 virus isolated from a human (A/Anhui/01/2013 [AH1]). The pulmonary viral loads, cytokine/chemokine profiles and histopathological changes of the infected mice were compared. The therapeutic efficacy of a non-steroidal anti-inflammatory drug (NSAID), celecoxib, was assessed. Results Without prior adaptation, intranasal inoculation of 106 plaque forming units (PFUs) of CK1 caused a mortality rate of 82% (14/17) in mice. Viral nucleoprotein and RNA expression were limited to the respiratory system and no viral RNA could be detected from brain, liver and kidney tissues. CK1 caused heavy alveolar inflammatory exudation and pulmonary hemorrhage, associated with high pulmonary levels of proinflammatory cytokines. In the mouse lung cell line LA-4, CK1 also induced high levels of interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) mRNA. Administration of the antiviral zanamivir did not significantly improve survival in mice infected with CK1, but co-administration of the non-steroidal anti-inflammatory drug (NSAID) celecoxib in combination with zanamivir improved survival and lung pathology. Conclusions Our findings suggested that H7N9 viruses isolated from chicken without preceding trans-species adaptation can cause lethal mammalian pulmonary infection. The severe proinflammatory responses might be a factor contributing to the mortality. Treatment with combination of antiviral and NSAID could ameliorate pulmonary inflammation and may improve survival.
Persistent Identifierhttp://hdl.handle.net/10722/217155
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, C-
dc.contributor.authorLi, CE-
dc.contributor.authorZhang, AJX-
dc.contributor.authorTo, KKW-
dc.contributor.authorLee, ACY-
dc.contributor.authorZhu, H-
dc.contributor.authorWu, HWL-
dc.contributor.authorChan, JFW-
dc.contributor.authorChen, H-
dc.contributor.authorHung, IFN-
dc.contributor.authorLi, L-
dc.contributor.authorYuen, KY-
dc.date.accessioned2015-09-18T05:49:55Z-
dc.date.available2015-09-18T05:49:55Z-
dc.date.issued2014-
dc.identifier.citationPLoS One, 2014, v. 9 n. 9, article no. e107966-
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10722/217155-
dc.description.abstractBackground Human infection caused by the avian influenza A H7N9 virus has a case-fatality rate of over 30%. Systematic study of the pathogenesis of avian H7N9 isolate and effective therapeutic strategies are needed. Methods BALB/c mice were inoculated intranasally with an H7N9 virus isolated from a chicken in a wet market epidemiologically linked to a fatal human case, (A/chicken/Zhejiang/DTID-ZJU01/2013 [CK1]), and with an H7N9 virus isolated from a human (A/Anhui/01/2013 [AH1]). The pulmonary viral loads, cytokine/chemokine profiles and histopathological changes of the infected mice were compared. The therapeutic efficacy of a non-steroidal anti-inflammatory drug (NSAID), celecoxib, was assessed. Results Without prior adaptation, intranasal inoculation of 106 plaque forming units (PFUs) of CK1 caused a mortality rate of 82% (14/17) in mice. Viral nucleoprotein and RNA expression were limited to the respiratory system and no viral RNA could be detected from brain, liver and kidney tissues. CK1 caused heavy alveolar inflammatory exudation and pulmonary hemorrhage, associated with high pulmonary levels of proinflammatory cytokines. In the mouse lung cell line LA-4, CK1 also induced high levels of interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) mRNA. Administration of the antiviral zanamivir did not significantly improve survival in mice infected with CK1, but co-administration of the non-steroidal anti-inflammatory drug (NSAID) celecoxib in combination with zanamivir improved survival and lung pathology. Conclusions Our findings suggested that H7N9 viruses isolated from chicken without preceding trans-species adaptation can cause lethal mammalian pulmonary infection. The severe proinflammatory responses might be a factor contributing to the mortality. Treatment with combination of antiviral and NSAID could ameliorate pulmonary inflammation and may improve survival.-
dc.languageeng-
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action-
dc.relation.ispartofPLoS One-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleAvian Influenza A H7N9 Virus Induces Severe Pneumonia in Mice without Prior Adaptation and Responds to a Combination of Zanamivir and COX-2 Inhibitor-
dc.typeArticle-
dc.identifier.emailZhang, AJX: zhangajx@hkucc.hku.hk-
dc.identifier.emailTo, KKW: kelvinto@hkucc.hku.hk-
dc.identifier.emailWu, HWL: hazelwu@hkucc.hku.hk-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailChen, H: hlchen@hku.hk-
dc.identifier.emailHung, IFN: ivanhung@hkucc.hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.authorityZhang, AJX=rp00413-
dc.identifier.authorityTo, KKW=rp01384-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authorityChen, H=rp00383-
dc.identifier.authorityHung, IFN=rp00508-
dc.identifier.authorityYuen, KY=rp00366-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0107966-
dc.identifier.pmid25232731-
dc.identifier.pmcidPMC4169509-
dc.identifier.scopuseid_2-s2.0-84907210256-
dc.identifier.hkuros252181-
dc.identifier.volume9-
dc.identifier.issue9-
dc.identifier.isiWOS:000342921200070-
dc.publisher.placeUnited States-

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