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Article: The aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a γδ T cell population in humanized mice

TitleThe aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a γδ T cell population in humanized mice
Authors
Issue Date2011
PublisherRockefeller University Press. The Journal's web site is located at http://www.jem.org
Citation
Journal Of Experimental Medicine, 2011, v. 208 n. 7, p. 1511-1522 How to Cite?
AbstractThere are few antiviral drugs for treating influenza, and the emergence of antiviral resistance has further limited the available therapeutic options. Furthermore, antivirals are not invariably effective in severe influenza, such as that caused by H5N1 viruses. Thus, there is an urgent need to develop alternative therapeutic strategies. Here, we show that human Vγ9Vδ2 T cells expanded by the aminobisphosphonate pamidronate (PAM) kill influenza virus-infected cells and inhibit viral replication in vitro. In Rag2-/-γc-/- immunodeficient mice reconstituted with human peripheral mononuclear cells (huPBMCs), PAM reduces disease severity and mortality caused by human seasonal H1N1 and avian H5N1 influenza virus, and controls the lung inflammation and viral replication. PAM has no such effects in influenza virus-infected Rag2-/-γc-/- mice reconstituted with Vγ9Vδ2 T cell-depleted huPBMCs. Our study provides proofof-concept of a novel therapeutic strategy for treating influenza by targeting the host rather than the virus, thereby reducing the opportunity for the emergence of drugresistant viruses. As PAM has been commonly used to treat osteoporosis and Paget's disease, this new application of an old drug potentially offers a safe and readily available option for treating influenza.
Persistent Identifierhttp://hdl.handle.net/10722/139524
ISSN
2015 Impact Factor: 11.24
2015 SCImago Journal Rankings: 10.762
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
University Grants Committee of the Hong Kong SAR, ChinaAoE/M-12/06
Research Fund for the Control of Infectious Diseases, Hong Kong SAR government07060482
Research Grants Council of Hong KongHKU 777108M
HKU777407
HKU768108
Funding Information:

This work was supported in part by the Area of Excellence program on Influenza supported by the University Grants Committee of the Hong Kong SAR, China (Project No AoE/M-12/06; J.S.M. Peiris, Y.-L. Lau, and W. Tu); the Research Fund for the Control of Infectious Diseases, Hong Kong SAR government (07060482; W. Tu); the General Research Fund, Research Grants Council of Hong Kong (HKU 777108M, HKU777407, and HKU768108; W. Tu and Y.-L. Lau).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorTu, Wen_HK
dc.contributor.authorZheng, Jen_HK
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorSia, SFen_HK
dc.contributor.authorLiu, Men_HK
dc.contributor.authorQin, Gen_HK
dc.contributor.authorNg, IHYen_HK
dc.contributor.authorXiang, Zen_HK
dc.contributor.authorLam, KTen_HK
dc.contributor.authorPeiris, JSMen_HK
dc.contributor.authorLau, YLen_HK
dc.date.accessioned2011-09-23T05:51:05Z-
dc.date.available2011-09-23T05:51:05Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal Of Experimental Medicine, 2011, v. 208 n. 7, p. 1511-1522en_HK
dc.identifier.issn0022-1007en_HK
dc.identifier.urihttp://hdl.handle.net/10722/139524-
dc.description.abstractThere are few antiviral drugs for treating influenza, and the emergence of antiviral resistance has further limited the available therapeutic options. Furthermore, antivirals are not invariably effective in severe influenza, such as that caused by H5N1 viruses. Thus, there is an urgent need to develop alternative therapeutic strategies. Here, we show that human Vγ9Vδ2 T cells expanded by the aminobisphosphonate pamidronate (PAM) kill influenza virus-infected cells and inhibit viral replication in vitro. In Rag2-/-γc-/- immunodeficient mice reconstituted with human peripheral mononuclear cells (huPBMCs), PAM reduces disease severity and mortality caused by human seasonal H1N1 and avian H5N1 influenza virus, and controls the lung inflammation and viral replication. PAM has no such effects in influenza virus-infected Rag2-/-γc-/- mice reconstituted with Vγ9Vδ2 T cell-depleted huPBMCs. Our study provides proofof-concept of a novel therapeutic strategy for treating influenza by targeting the host rather than the virus, thereby reducing the opportunity for the emergence of drugresistant viruses. As PAM has been commonly used to treat osteoporosis and Paget's disease, this new application of an old drug potentially offers a safe and readily available option for treating influenza.en_HK
dc.languageengen_US
dc.publisherRockefeller University Press. The Journal's web site is located at http://www.jem.orgen_HK
dc.relation.ispartofJournal of Experimental Medicineen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAntiviral Agents - pharmacology-
dc.subject.meshCytotoxicity, Immunologic-
dc.subject.meshDiphosphonates - pharmacology-
dc.subject.meshOrthomyxoviridae Infections - drug therapy - immunology - pathology-
dc.subject.meshT-Lymphocyte Subsets - drug effects - immunology-
dc.titleThe aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a γδ T cell population in humanized miceen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-1007&volume=208&issue=7&spage=1511&epage=1522&date=2011&atitle=The+aminobisphosphonate+pamidronate+controls+influenza+pathogenesis+by+expanding+a+gammadelta+T+cell+population+in+humanized+mice-
dc.identifier.emailTu, W: wwtu@hku.hken_HK
dc.identifier.emailLiu, Y: yinpingl@hku.hken_HK
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hken_HK
dc.identifier.emailLau, YL: lauylung@hku.hken_HK
dc.identifier.authorityTu, W=rp00416en_HK
dc.identifier.authorityLiu, Y=rp00269en_HK
dc.identifier.authorityPeiris, JSM=rp00410en_HK
dc.identifier.authorityLau, YL=rp00361en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1084/jem.20110226en_HK
dc.identifier.pmid21708931-
dc.identifier.pmcidPMC3135369-
dc.identifier.scopuseid_2-s2.0-79960360772en_HK
dc.identifier.hkuros195984en_US
dc.identifier.hkuros191483-
dc.identifier.hkuros200732-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79960360772&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume208en_HK
dc.identifier.issue7en_HK
dc.identifier.spage1511en_HK
dc.identifier.epage1522en_HK
dc.identifier.eissn1540-9538-
dc.identifier.isiWOS:000292637000016-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f100012807956-
dc.relation.projectControl of Pandemic and Inter-pandemic Influenza-
dc.relation.projectHumanized mouse as a model to study the antiviral activity of human gammadelta-T cells against human and avian influenza A viruses in vivo-
dc.relation.projectThe Role of Natural Killer Cells in the Pathogenesis of Avian Influenza Virus Infection-
dc.identifier.scopusauthoridTu, W=7006479236en_HK
dc.identifier.scopusauthoridZheng, J=55217878700en_HK
dc.identifier.scopusauthoridLiu, Y=35240639600en_HK
dc.identifier.scopusauthoridSia, SF=8574447900en_HK
dc.identifier.scopusauthoridLiu, M=55210686600en_HK
dc.identifier.scopusauthoridQin, G=35085420900en_HK
dc.identifier.scopusauthoridNg, IHY=8671050800en_HK
dc.identifier.scopusauthoridXiang, Z=37032263900en_HK
dc.identifier.scopusauthoridLam, KT=25630903400en_HK
dc.identifier.scopusauthoridPeiris, JSM=7005486823en_HK
dc.identifier.scopusauthoridLau, YL=7201403380en_HK

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