{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:56:57Z","timestamp":1787587017420,"version":"build-2736575974"},"reference-count":21,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T00:00:00Z","timestamp":1552867200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T00:00:00Z","timestamp":1552867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["FT120100876"],"award-info":[{"award-number":["FT120100876"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1122506"],"award-info":[{"award-number":["1122506"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1128276"],"award-info":[{"award-number":["1128276"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Respirology"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and objective<\/jats:title>\n                    <jats:p>Influenza A viruses (IAV) cause respiratory tract infections that can be fatal when the virus spreads to the alveolar space (i.e. alveolitis), and this is mainly observed with highly pathogenic strains. Reactive oxygen species (ROS) production by the NOX2 NADPH oxidase in endosomes has been directly implicated in IAV pathology. Recently, we demonstrated that treatment with a novel endosome\u2010targeted NOX2 oxidase inhibitor, cholestanol\u2010conjugated gp91dsTAT (Cgp91ds\u2010TAT), attenuated airway inflammation and viral replication to infection with a low pathogenic influenza A viral strain. Here, we determined whether suppression of endosome NOX2 oxidase prevents the lung inflammation following infection with a highly pathogenic IAV strain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>C57Bl\/6 mice were intranasally treated with either DMSO vehicle (2%) or Cgp91ds\u2010TAT (0.2\u2009mg\/kg\/day) 1 day prior to infection with the high pathogenicity PR8 IAV strain (500\u2009PFU\/mouse). At Day 3 post\u2010infection, mice were culled for the evaluation of airway and lung inflammation, viral titres and ROS generation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PR8 infection resulted in a marked degree of airway inflammation, epithelial denudation, alveolitis and inflammatory cell ROS production. Cgp91ds\u2010TAT treatment significantly attenuated airway inflammation, including neutrophil influx, the degree of alveolitis and inflammatory cell ROS generation. Importantly, the anti\u2010inflammatory phenotype affected by Cgp91ds\u2010TAT significantly enhanced the clearance of lung viral mRNA following PR8 infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Endosomal NOX2 oxidase promotes pathogenic lung inflammation to IAV infection. The localized delivery of endosomal NOX2 oxidase inhibitors is a novel therapeutic strategy against IAV, which has the potential to limit the pathogenesis caused during epidemics and pandemics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/resp.13524","type":"journal-article","created":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T23:52:51Z","timestamp":1552953171000},"page":"1011-1017","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Novel endosomal NOX2 oxidase inhibitor ameliorates pandemic influenza A virus\u2010induced lung inflammation in mice"],"prefix":"10.1111","volume":"24","author":[{"given":"Eunice E.","family":"To","sequence":"first","affiliation":[{"name":"School of Health Sciences and Biomedical Sciences RMIT University  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Luong","sequence":"additional","affiliation":[{"name":"School of Health Sciences and Biomedical Sciences RMIT University  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayin","family":"Diao","sequence":"additional","affiliation":[{"name":"Monash Institute of Pharmaceutical Sciences Monash University  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"O\u2019 Leary","sequence":"additional","affiliation":[{"name":"Sir Patrick Dun's Laboratory, Central Pathology Laboratory St James's Hospital  Dublin Ireland"},{"name":"Emer Casey Research Laboratory, Molecular Pathology Laboratory The Coombe Women and Infants University Hospital  Dublin Ireland"},{"name":"CERVIVA Research Consortium Trinity College  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doug A.","family":"Brooks","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Sciences, Division of Health Sciences University of South Australia  Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8443-7071","authenticated-orcid":false,"given":"Ross","family":"Vlahos","sequence":"additional","affiliation":[{"name":"School of Health Sciences and Biomedical Sciences RMIT University  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3989-7615","authenticated-orcid":false,"given":"Stavros","family":"Selemidis","sequence":"additional","affiliation":[{"name":"School of Health Sciences and Biomedical Sciences RMIT University  Melbourne VIC Australia"},{"name":"Department of Pharmacology, Infection and Immunity Program, Biomedicine Discovery Institute Monash University  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra050740"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3854"},{"key":"e_1_2_7_4_1","first-page":"1087","article-title":"Treatment and prophylaxis of influenza and the problem of resistance to neuraminidase inhibitors","volume":"69","author":"Nitsch\u2010Osuch A","year":"2015","journal-title":"Postepy Hig. 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