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Article: Cytotoxic T lymphocytes established by seasonal human influenza cross-react against 2009 pandemic H1N1 influenza virus

TitleCytotoxic T lymphocytes established by seasonal human influenza cross-react against 2009 pandemic H1N1 influenza virus
Authors
Issue Date2010
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
Citation
Journal Of Virology, 2010, v. 84 n. 13, p. 6527-6535 How to Cite?
AbstractWhile few children and young adults have cross-protective antibodies to the pandemic H1N1 2009 (pdmH1N1) virus, the illness remains mild. The biological reasons for these epidemiological observations are unclear. In this study, we demonstrate that the bulk memory cytotoxic T lymphocytes (CTLs) established by seasonal influenza viruses from healthy individuals who have not been exposed to pdmH1N1 can directly lyse pdmH1N1-infected target cells and produce gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). Using influenza A virus matrix protein 1 (M1 58-66) epitope-specific CTLs isolated from healthy HLA-A2 + individuals, we further found that M1 58-66 epitope-specific CTLs efficiently killed both M1 58-66 peptide-pulsed and pdmH1N1-infected target cells ex vivo. These M1 58-66-specific CTLs showed an effector memory phenotype and expressed CXCR3 and CCR5 chemokine receptors. Of 94 influenza A virus CD8 T-cell epitopes obtained from the Immune Epitope Database (IEDB), 17 epitopes are conserved in pdmH1N1, and more than half of these conserved epitopes are derived from M1 protein. In addition, 65% (11/17) of these epitopes were 100% conserved in seasonal influenza vaccine H1N1 strains during the last 20 years. Importantly, seasonal influenza vaccination could expand the functional M1 58-66 epitope-specific CTLs in 20% (4/20) of HLA-A2 + individuals. Our results indicated that memory CTLs established by seasonal influenza A viruses or vaccines had cross-reactivity against pdmH1N1. These might explain, at least in part, the unexpected mild pdmH1N1 illness in the community and also might provide some valuable insights for the future design of broadly protective vaccines to prevent influenza, especially pandemic influenza. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Persistent Identifierhttp://hdl.handle.net/10722/125229
ISSN
2015 Impact Factor: 4.606
2015 SCImago Journal Rankings: 3.347
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
University Grants Committee of the Hong Kong Special Administrative Region, ChinaAoE/M-12/06
Research Grants Council of Hong KongHKU 777108 M
HKU777407
HKU768108
Research Fund for the Control of Infectious Diseases, Hong Kong SAR government07060482
University Research Committee, the University of Hong Kong200611159224
University of Hong Kong
Edward Sai-Kim Hotung Pediatric Education and Research Fund
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 Special Administrative Region, China (project no. AoE/M-12/06) (J.S.M.P., Y.-L.L., and W. T.); the General Research Fund, Research Grants Council of Hong Kong (HKU 777108 M, HKU777407, and HKU768108) (W. T. and Y.-L.L.); the Research Fund for the Control of Infectious Diseases, Hong Kong SAR government (07060482) (W. T.); Seed Funding for Basic Research, University Research Committee, the University of Hong Kong (200611159224) (W. T.); postgraduate studentships, University of Hong Kong (H. M., G. Q., and J. Z.); and the Edward Sai-Kim Hotung Pediatric Education and Research Fund (Y.-L.L.).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorTu, Wen_HK
dc.contributor.authorMao, Hen_HK
dc.contributor.authorZheng, Jen_HK
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorChiu, SSen_HK
dc.contributor.authorQin, Gen_HK
dc.contributor.authorChan, PLen_HK
dc.contributor.authorLam, KTen_HK
dc.contributor.authorGuan, Jen_HK
dc.contributor.authorZhang, Len_HK
dc.contributor.authorGuan, Yen_HK
dc.contributor.authorYuen, KYen_HK
dc.contributor.authorPeiris, JSMen_HK
dc.contributor.authorLau, YLen_HK
dc.date.accessioned2010-10-31T11:18:48Z-
dc.date.available2010-10-31T11:18:48Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Virology, 2010, v. 84 n. 13, p. 6527-6535en_HK
dc.identifier.issn0022-538Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/125229-
dc.description.abstractWhile few children and young adults have cross-protective antibodies to the pandemic H1N1 2009 (pdmH1N1) virus, the illness remains mild. The biological reasons for these epidemiological observations are unclear. In this study, we demonstrate that the bulk memory cytotoxic T lymphocytes (CTLs) established by seasonal influenza viruses from healthy individuals who have not been exposed to pdmH1N1 can directly lyse pdmH1N1-infected target cells and produce gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). Using influenza A virus matrix protein 1 (M1 58-66) epitope-specific CTLs isolated from healthy HLA-A2 + individuals, we further found that M1 58-66 epitope-specific CTLs efficiently killed both M1 58-66 peptide-pulsed and pdmH1N1-infected target cells ex vivo. These M1 58-66-specific CTLs showed an effector memory phenotype and expressed CXCR3 and CCR5 chemokine receptors. Of 94 influenza A virus CD8 T-cell epitopes obtained from the Immune Epitope Database (IEDB), 17 epitopes are conserved in pdmH1N1, and more than half of these conserved epitopes are derived from M1 protein. In addition, 65% (11/17) of these epitopes were 100% conserved in seasonal influenza vaccine H1N1 strains during the last 20 years. Importantly, seasonal influenza vaccination could expand the functional M1 58-66 epitope-specific CTLs in 20% (4/20) of HLA-A2 + individuals. Our results indicated that memory CTLs established by seasonal influenza A viruses or vaccines had cross-reactivity against pdmH1N1. These might explain, at least in part, the unexpected mild pdmH1N1 illness in the community and also might provide some valuable insights for the future design of broadly protective vaccines to prevent influenza, especially pandemic influenza. Copyright © 2010, American Society for Microbiology. All Rights Reserved.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/en_HK
dc.relation.ispartofJournal of Virologyen_HK
dc.rightsJournal of Virology. Copyright © American Society for Microbiology.-
dc.rightsCopyright © American Society for Microbiology, Journal of Virology, 2010, v. 84 n. 13, p. 6527-6535-
dc.subject.meshCross Protection-
dc.subject.meshCross Reactions-
dc.subject.meshInfluenza A Virus, H1N1 Subtype - immunology-
dc.subject.meshInfluenza, Human - epidemiology - immunology - virology-
dc.subject.meshT-Lymphocytes, Cytotoxic - immunology-
dc.titleCytotoxic T lymphocytes established by seasonal human influenza cross-react against 2009 pandemic H1N1 influenza virusen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-538X&volume=84&issue=13&spage=6527&epage=6535&date=2010&atitle=Cytotoxic+T+Lymphocytes+Established+by+Seasonal+Human+Influenza+Cross-react+against+2009+Pandemic+H1N1+Influenza+Virus.en_HK
dc.identifier.emailTu, W: wwtu@hku.hken_HK
dc.identifier.emailMao, H: hwmau@hku.hken_HK
dc.identifier.emailLiu, Y: yinpingl@hku.hken_HK
dc.identifier.emailChiu, SS: ssschiu@hku.hken_HK
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hken_HK
dc.identifier.emailYuen, KY: kyyuen@hkucc.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.authorityMao, H=rp01595en_HK
dc.identifier.authorityLiu, Y=rp00269en_HK
dc.identifier.authorityChiu, SS=rp00421en_HK
dc.identifier.authorityGuan, Y=rp00397en_HK
dc.identifier.authorityYuen, KY=rp00366en_HK
dc.identifier.authorityPeiris, JSM=rp00410en_HK
dc.identifier.authorityLau, YL=rp00361en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1128/JVI.00519-10en_HK
dc.identifier.pmid20410263-
dc.identifier.pmcidPMC2903266-
dc.identifier.scopuseid_2-s2.0-77953295181en_HK
dc.identifier.hkuros179353en_HK
dc.identifier.hkuros179388-
dc.identifier.hkuros170444-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77953295181&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume84en_HK
dc.identifier.issue13en_HK
dc.identifier.spage6527en_HK
dc.identifier.epage6535en_HK
dc.identifier.isiWOS:000278551900025-
dc.publisher.placeUnited Statesen_HK
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.projectControl of Pandemic and Inter-pandemic Influenza-
dc.identifier.scopusauthoridTu, W=7006479236en_HK
dc.identifier.scopusauthoridMao, H=25632489000en_HK
dc.identifier.scopusauthoridZheng, J=55217878700en_HK
dc.identifier.scopusauthoridLiu, Y=35240639600en_HK
dc.identifier.scopusauthoridChiu, SS=7202291500en_HK
dc.identifier.scopusauthoridQin, G=35085420900en_HK
dc.identifier.scopusauthoridChan, PL=25631876900en_HK
dc.identifier.scopusauthoridLam, KT=25630903400en_HK
dc.identifier.scopusauthoridGuan, J=36243371100en_HK
dc.identifier.scopusauthoridZhang, L=14046384200en_HK
dc.identifier.scopusauthoridGuan, Y=7202924055en_HK
dc.identifier.scopusauthoridYuen, KY=36078079100en_HK
dc.identifier.scopusauthoridPeiris, JSM=7005486823en_HK
dc.identifier.scopusauthoridLau, YL=7201403380en_HK

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