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Article: The Therapeutic Effect of Pamidronate on Lethal Avian Influenza A H7N9 Virus Infected Humanized Mice

TitleThe Therapeutic Effect of Pamidronate on Lethal Avian Influenza A H7N9 Virus Infected Humanized Mice
Authors
Issue Date2015
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
PLoS One, 2015, v. 10 n. 8, p. Article No. e0135999 How to Cite?
AbstractA novel avian influenza virus H7N9 infection occurred among human populations since 2013. Although the lack of sustained human-to-human transmission limited the epidemics caused by H7N9, the late presentation of most patients and the emergence of neuraminidase-resistant strains made the development of novel antiviral strategy against H7N9 in urgent demands. In this study, we evaluated the potential of pamidronate, a pharmacological phosphoantigen that can specifically boost human Vδ2-T-cell, on treating H7N9 virus-infected humanized mice. Our results showed that intraperitoneal injection of pamidronate could potently decrease the morbidity and mortality of H7N9-infected mice through controlling both viral replication and inflammation in affected lungs. More importantly, pamidronate treatment starting from 3 days after infection could still significantly ameliorate the severity of diseases in infected mice and improve their survival chance, whereas orally oseltamivir treatment starting at the same time showed no therapeutic effects. As for the mechanisms underlying pamidronate-based therapy, our in vitro data demonstrated that its antiviral effects were partly mediated by IFN-γ secreted from human Vδ2-T cells. Meanwhile, human Vδ2-T cells could directly kill virus-infected host cells in a perforin-, granzyme B- and CD137-dependent manner. As pamidronate has been used for osteoporosis treatment for more than 20 years, pamidronate-based therapy represents for a safe and readily available option for clinical trials to treat H7N9 infection.
Persistent Identifierhttp://hdl.handle.net/10722/218794
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
ISI Accession Number ID
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DC FieldValueLanguage
dc.contributor.authorZheng, J-
dc.contributor.authorWu, WL-
dc.contributor.authorLiu, YP-
dc.contributor.authorZheng, X-
dc.contributor.authorLiu, M-
dc.contributor.authorChan, KH-
dc.contributor.authorLau, SY-
dc.contributor.authorLam, KT-
dc.contributor.authorTo, KKW-
dc.contributor.authorChan, JFW-
dc.contributor.authorLi, LJ-
dc.contributor.authorChen, HL-
dc.contributor.authorLau, YL-
dc.contributor.authorYuen, KY-
dc.contributor.authorTu, WW-
dc.date.accessioned2015-09-18T06:53:38Z-
dc.date.available2015-09-18T06:53:38Z-
dc.date.issued2015-
dc.identifier.citationPLoS One, 2015, v. 10 n. 8, p. Article No. e0135999-
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10722/218794-
dc.description.abstractA novel avian influenza virus H7N9 infection occurred among human populations since 2013. Although the lack of sustained human-to-human transmission limited the epidemics caused by H7N9, the late presentation of most patients and the emergence of neuraminidase-resistant strains made the development of novel antiviral strategy against H7N9 in urgent demands. In this study, we evaluated the potential of pamidronate, a pharmacological phosphoantigen that can specifically boost human Vδ2-T-cell, on treating H7N9 virus-infected humanized mice. Our results showed that intraperitoneal injection of pamidronate could potently decrease the morbidity and mortality of H7N9-infected mice through controlling both viral replication and inflammation in affected lungs. More importantly, pamidronate treatment starting from 3 days after infection could still significantly ameliorate the severity of diseases in infected mice and improve their survival chance, whereas orally oseltamivir treatment starting at the same time showed no therapeutic effects. As for the mechanisms underlying pamidronate-based therapy, our in vitro data demonstrated that its antiviral effects were partly mediated by IFN-γ secreted from human Vδ2-T cells. Meanwhile, human Vδ2-T cells could directly kill virus-infected host cells in a perforin-, granzyme B- and CD137-dependent manner. As pamidronate has been used for osteoporosis treatment for more than 20 years, pamidronate-based therapy represents for a safe and readily available option for clinical trials to treat H7N9 infection.-
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.titleThe Therapeutic Effect of Pamidronate on Lethal Avian Influenza A H7N9 Virus Infected Humanized Mice-
dc.typeArticle-
dc.identifier.emailZheng, J: teddy629@hku.hk-
dc.identifier.emailLiu, YP: yinpingl@hku.hk-
dc.identifier.emailChan, KH: chankh2@hkucc.hku.hk-
dc.identifier.emailLam, KT: ktlama@graduate.hku.hk-
dc.identifier.emailTo, KKW: kelvinto@HKUCC.hku.hk-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailChen, HL: hlchen@hku.hk-
dc.identifier.emailLau, YL: lauylung@hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hku.hk-
dc.identifier.emailTu, WW: wwtu@hku.hk-
dc.identifier.authorityZheng, J=rp02004-
dc.identifier.authorityLiu, YP=rp00269-
dc.identifier.authorityTo, KKW=rp01384-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authorityChen, HL=rp00383-
dc.identifier.authorityLau, YL=rp00361-
dc.identifier.authorityYuen, KY=rp00366-
dc.identifier.authorityTu, WW=rp00416-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0135999-
dc.identifier.pmid26285203-
dc.identifier.scopuseid_2-s2.0-84942437126-
dc.identifier.hkuros250301-
dc.identifier.volume10-
dc.identifier.issue8-
dc.identifier.spageArticle No. e0135999-
dc.identifier.epageArticle No. e0135999-
dc.identifier.isiWOS:000359666100095-
dc.publisher.placeUnited States-
dc.relation.projectRole of human gammadelta-T cells in the generation of influenza virus-specific antibody-
dc.relation.projectControl of Pandemic and Inter-pandemic Influenza-

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