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Article: Inhibition of human natural killer cell activity by influenza virions and hemagglutinin

TitleInhibition of human natural killer cell activity by influenza virions and hemagglutinin
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. 9, p. 4148-4157 How to Cite?
AbstractNatural killer (NK) cells keep viral infections under control at the early phase by directly killing infected cells. Influenza is an acute contagious respiratory viral disease transmitted from host-to-host in the first few days of infection. The evasion of host innate immune defenses including NK cells is important for its success as a viral pathogen of humans and animals. NK cells encounter influenza virus within the microenvironment of infected cells. It therefore is important to investigate the direct effects of influenza virus on NK cell activity. Recently we demonstrated that influenza virus directly infects human NK cells and induces cell apoptosis to counter their function (H. Mao, W. Tu, G. Qin, H. K. W. Law, S. F. Sia, P.-L. Chan, Y. Liu, K.-T. Lam, J. Zheng, M. Peiris, and Y.-L. Lau, J. Virol. 83:9215-9222, 2009). Here, we further demonstrated that both the intact influenza virion and free hemagglutinin protein inhibited the cytotoxicity of fresh and interleukin-2 (IL-2)-activated primary human NK cells. Hemagglutinin bound and internalized into NK cells via the sialic acids. This interaction did not decrease NKp46 expression but caused the downregulation of the ζ chain through the lysosomal pathway, which caused the decrease of NK cell cytotoxicity mediated by NKp46 and NKp30. The underlying dysregulation of the signaling pathway involved ζ chain downregulation, leading to decreased Syk and ERK activation and granule exocytosis upon target cell stimulation, finally causing reduced cytotoxicity. These findings suggest that influenza virus developed a novel strategy to evade NK cell innate immune defense that is likely to facilitate viral transmission and also contribute to virus pathogenesis. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Persistent Identifierhttp://hdl.handle.net/10722/125237
ISSN
2015 Impact Factor: 4.606
2015 SCImago Journal Rankings: 3.347
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
General Research Fund, Research Grants Council of Hong KongHKU 777108 M
HKU768108
HKU777407
University Grants Committee of the Hong Kong Special Administrative Region, ChinaAoE/M-12/06
University of Hong Kong200611159224
Edward Sai-Kim Hotung Pediatric Education and Research Fund
Funding Information:

This work was supported in part by the General Research Fund, Research Grants Council of Hong Kong (HKU 777108 M, HKU768108, HKU777407; W. T. and Y.-L.L.); 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.); Seed Funding for Basic Research, University Research Committee, the University of Hong Kong (200611159224; W. T.); postgraduate studentships from the 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.authorMao, Hen_HK
dc.contributor.authorTu, Wen_HK
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorQin, Gen_HK
dc.contributor.authorZheng, Jen_HK
dc.contributor.authorChan, PLen_HK
dc.contributor.authorLam, KTen_HK
dc.contributor.authorMalik Peiris, JSen_HK
dc.contributor.authorLau, YLen_HK
dc.date.accessioned2010-10-31T11:19:15Z-
dc.date.available2010-10-31T11:19:15Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Virology, 2010, v. 84 n. 9, p. 4148-4157en_HK
dc.identifier.issn0022-538Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/125237-
dc.description.abstractNatural killer (NK) cells keep viral infections under control at the early phase by directly killing infected cells. Influenza is an acute contagious respiratory viral disease transmitted from host-to-host in the first few days of infection. The evasion of host innate immune defenses including NK cells is important for its success as a viral pathogen of humans and animals. NK cells encounter influenza virus within the microenvironment of infected cells. It therefore is important to investigate the direct effects of influenza virus on NK cell activity. Recently we demonstrated that influenza virus directly infects human NK cells and induces cell apoptosis to counter their function (H. Mao, W. Tu, G. Qin, H. K. W. Law, S. F. Sia, P.-L. Chan, Y. Liu, K.-T. Lam, J. Zheng, M. Peiris, and Y.-L. Lau, J. Virol. 83:9215-9222, 2009). Here, we further demonstrated that both the intact influenza virion and free hemagglutinin protein inhibited the cytotoxicity of fresh and interleukin-2 (IL-2)-activated primary human NK cells. Hemagglutinin bound and internalized into NK cells via the sialic acids. This interaction did not decrease NKp46 expression but caused the downregulation of the ζ chain through the lysosomal pathway, which caused the decrease of NK cell cytotoxicity mediated by NKp46 and NKp30. The underlying dysregulation of the signaling pathway involved ζ chain downregulation, leading to decreased Syk and ERK activation and granule exocytosis upon target cell stimulation, finally causing reduced cytotoxicity. These findings suggest that influenza virus developed a novel strategy to evade NK cell innate immune defense that is likely to facilitate viral transmission and also contribute to virus pathogenesis. 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, [insert journal name, volume number, page numbers, and year]-
dc.subject.meshCells, Cultured-
dc.subject.meshHemagglutinins, Viral - immunology-
dc.subject.meshInfluenza A Virus, H1N1 Subtype - immunology - pathogenicity-
dc.subject.meshKiller Cells, Natural - immunology - virology-
dc.subject.meshVirion - immunology-
dc.titleInhibition of human natural killer cell activity by influenza virions and hemagglutininen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-538X&volume=84&issue=9&spage=4148&epage=4157&date=2010&atitle=Inhibition+of+human+natural+killer+cell+activity+by+influenza+virions+and+hemagglutininen_HK
dc.identifier.emailMao, H: hwmau@hku.hken_HK
dc.identifier.emailTu, W: wwtu@hku.hken_HK
dc.identifier.emailLiu, Y: yinpingl@hku.hken_HK
dc.identifier.emailMalik Peiris, JS: malik@hkucc.hku.hken_HK
dc.identifier.emailLau, YL: lauylung@hku.hken_HK
dc.identifier.authorityMao, H=rp01595en_HK
dc.identifier.authorityTu, W=rp00416en_HK
dc.identifier.authorityLiu, Y=rp00269en_HK
dc.identifier.authorityMalik Peiris, JS=rp00410en_HK
dc.identifier.authorityLau, YL=rp00361en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1128/JVI.02340-09en_HK
dc.identifier.pmid20164232-
dc.identifier.pmcidPMC2863726-
dc.identifier.scopuseid_2-s2.0-77950828696en_HK
dc.identifier.hkuros170380en_HK
dc.identifier.hkuros179386-
dc.identifier.hkuros192245-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77950828696&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume84en_HK
dc.identifier.issue9en_HK
dc.identifier.spage4148en_HK
dc.identifier.epage4157en_HK
dc.identifier.eissn1098-5514-
dc.identifier.isiWOS:000276358000004-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectControl of Pandemic and Inter-pandemic Influenza-
dc.identifier.scopusauthoridMao, H=25632489000en_HK
dc.identifier.scopusauthoridTu, W=7006479236en_HK
dc.identifier.scopusauthoridLiu, Y=35240639600en_HK
dc.identifier.scopusauthoridQin, G=35085420900en_HK
dc.identifier.scopusauthoridZheng, J=55217878700en_HK
dc.identifier.scopusauthoridChan, PL=25631876900en_HK
dc.identifier.scopusauthoridLam, KT=25630903400en_HK
dc.identifier.scopusauthoridMalik Peiris, JS=7005486823en_HK
dc.identifier.scopusauthoridLau, YL=7201403380en_HK
dc.identifier.citeulike7660235-

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