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Article: Avian influenza H5N1 virus induces cytopathy and proinflammatory cytokine responses in human astrocytic and neuronal cell lines

TitleAvian influenza H5N1 virus induces cytopathy and proinflammatory cytokine responses in human astrocytic and neuronal cell lines
Authors
KeywordsCytokine
Influenza virus
Neurodegenerative disease
Neuroinflammation
Viral infection
Issue Date2010
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/neuroscience
Citation
Neuroscience, 2010, v. 168 n. 3, p. 613-623 How to Cite?
AbstractIt has previously been reported that the avian H5N1 type of influenza A virus can be detected in neurons and astrocytes of human brains in autopsy cases. However, the underlying neuropathogenicity remains unexplored. In this study, we used differentiated human astrocytic and neuronal cell lines as models to examine the effect of H5N1 influenza A viral infection on the viral growth kinetics and immune responses of the infected cells. We found that the influenza virus receptors, sialic acid-2,3-galactose and sialic acid-2,6-galactose, were expressed on differentiated human astrocytic and neuronal cells. Both types of cells could be infected with H5N1 influenza A viruses, but progeny viruses were only produced from infected astrocytic cells but not neuronal cells. Moreover, increased expression of interleukin (IL)-6 and/or tumor necrosis factor (TNF-) mRNA was detected in both astrocytic and neuronal cells at 6 and 24 h post-infection. To examine the biological consequences of such enhanced cytokine expression, differentiated astrocytic and neuronal cells were directly treated with these two cytokines. TNF- treatment induced apoptosis, as well as proinflammatory cytokine, chemokine and inflammatory responses in differentiated astrocytic and neuronal cells. Taken together, our findings reveal that avian influenza H5N1 viruses can infect human astrocytic and neuronal cells, resulting in the induction of direct cellular damage and proinflammatory cytokine cascades. Our observations suggest that avian influenza H5N1 infection can trigger profound CNS injury, which may play an important role in the influenza viral pathogenesis. © 2010 IBRO.
Persistent Identifierhttp://hdl.handle.net/10722/141720
ISSN
2023 Impact Factor: 2.9
2023 SCImago Journal Rankings: 0.903
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of Hong Kong SARHKUST 1/06C
HKU 1/05C
Area of Excellence Scheme of the University Grants CommitteeAoE/B-15/01
AoE/M-12/06
Hong Kong Jockey Club
Funding Information:

We would like to acknowledge Cynthia lp for technical assistance and Drs KO Lai, Zelda Cheung and Amy Fu for helpful discussion. This work was supported in part by the Research Grants Council of Hong Kong SAR (HKUST 1/06C, HKU 1/05C), Area of Excellence Scheme of the University Grants Committee (AoE/B-15/01 and AoE/M-12/06) and Hong Kong Jockey Club.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorNg, YPen_HK
dc.contributor.authorLee, SMYen_HK
dc.contributor.authorCheung, TKWen_HK
dc.contributor.authorNicholls, JMen_HK
dc.contributor.authorPeiris, JSMen_HK
dc.contributor.authorIp, NYen_HK
dc.date.accessioned2011-09-27T02:59:11Z-
dc.date.available2011-09-27T02:59:11Z-
dc.date.issued2010en_HK
dc.identifier.citationNeuroscience, 2010, v. 168 n. 3, p. 613-623en_HK
dc.identifier.issn0306-4522en_HK
dc.identifier.urihttp://hdl.handle.net/10722/141720-
dc.description.abstractIt has previously been reported that the avian H5N1 type of influenza A virus can be detected in neurons and astrocytes of human brains in autopsy cases. However, the underlying neuropathogenicity remains unexplored. In this study, we used differentiated human astrocytic and neuronal cell lines as models to examine the effect of H5N1 influenza A viral infection on the viral growth kinetics and immune responses of the infected cells. We found that the influenza virus receptors, sialic acid-2,3-galactose and sialic acid-2,6-galactose, were expressed on differentiated human astrocytic and neuronal cells. Both types of cells could be infected with H5N1 influenza A viruses, but progeny viruses were only produced from infected astrocytic cells but not neuronal cells. Moreover, increased expression of interleukin (IL)-6 and/or tumor necrosis factor (TNF-) mRNA was detected in both astrocytic and neuronal cells at 6 and 24 h post-infection. To examine the biological consequences of such enhanced cytokine expression, differentiated astrocytic and neuronal cells were directly treated with these two cytokines. TNF- treatment induced apoptosis, as well as proinflammatory cytokine, chemokine and inflammatory responses in differentiated astrocytic and neuronal cells. Taken together, our findings reveal that avian influenza H5N1 viruses can infect human astrocytic and neuronal cells, resulting in the induction of direct cellular damage and proinflammatory cytokine cascades. Our observations suggest that avian influenza H5N1 infection can trigger profound CNS injury, which may play an important role in the influenza viral pathogenesis. © 2010 IBRO.en_HK
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/neuroscienceen_HK
dc.relation.ispartofNeuroscienceen_HK
dc.subjectCytokineen_HK
dc.subjectInfluenza virusen_HK
dc.subjectNeurodegenerative diseaseen_HK
dc.subjectNeuroinflammationen_HK
dc.subjectViral infectionen_HK
dc.subject.meshApoptosisen_HK
dc.subject.meshAstrocytes - cytology - immunology - virologyen_HK
dc.subject.meshCell Differentiationen_HK
dc.subject.meshCell Lineen_HK
dc.subject.meshChemokine CCL2 - biosynthesisen_HK
dc.subject.meshCyclooxygenase 2 - biosynthesisen_HK
dc.subject.meshCytokines - metabolismen_HK
dc.subject.meshCytopathogenic Effect, Viralen_HK
dc.subject.meshGalactose - analogs & derivatives - biosynthesisen_HK
dc.subject.meshHumansen_HK
dc.subject.meshInfluenza A Virus, H1N1 Subtype - physiologyen_HK
dc.subject.meshInfluenza A Virus, H5N1 Subtype - physiologyen_HK
dc.subject.meshInterleukin-6 - biosynthesis - geneticsen_HK
dc.subject.meshNeurons - cytology - immunology - virologyen_HK
dc.subject.meshRNA, Messenger - biosynthesisen_HK
dc.subject.meshReceptors, Virus - biosynthesisen_HK
dc.subject.meshTumor Necrosis Factor-alpha - biosynthesis - geneticsen_HK
dc.titleAvian influenza H5N1 virus induces cytopathy and proinflammatory cytokine responses in human astrocytic and neuronal cell linesen_HK
dc.typeArticleen_HK
dc.identifier.emailLee, SMY: suki@hku.hken_HK
dc.identifier.emailNicholls, JM: jmnichol@hkucc.hku.hken_HK
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hken_HK
dc.identifier.authorityLee, SMY=rp01536en_HK
dc.identifier.authorityNicholls, JM=rp00364en_HK
dc.identifier.authorityPeiris, JSM=rp00410en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.neuroscience.2010.04.013en_HK
dc.identifier.pmid20398740-
dc.identifier.scopuseid_2-s2.0-77953119857en_HK
dc.identifier.hkuros171559-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77953119857&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume168en_HK
dc.identifier.issue3en_HK
dc.identifier.spage613en_HK
dc.identifier.epage623en_HK
dc.identifier.eissn1873-7544-
dc.identifier.isiWOS:000278611500003-
dc.publisher.placeNetherlandsen_HK
dc.relation.projectPathogenesis, cell signaling and virus evolution of avian influenza A (H5N1)-
dc.relation.projectControl of Pandemic and Inter-pandemic Influenza-
dc.identifier.scopusauthoridNg, YP=7202471018en_HK
dc.identifier.scopusauthoridLee, SMY=35435155600en_HK
dc.identifier.scopusauthoridCheung, TKW=16229531100en_HK
dc.identifier.scopusauthoridNicholls, JM=7201463077en_HK
dc.identifier.scopusauthoridPeiris, JSM=7005486823en_HK
dc.identifier.scopusauthoridIp, NY=7005756760en_HK
dc.identifier.citeulike7055300-
dc.identifier.issnl0306-4522-

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