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Conference Paper: Polarity of influenza H5N1 virus infection in respiratory epithelial cells and the impact of basolateral release of cytokines in disease pathogenesis

TitlePolarity of influenza H5N1 virus infection in respiratory epithelial cells and the impact of basolateral release of cytokines in disease pathogenesis
Authors
Issue Date2007
PublisherInternational Medical Press Ltd.
Citation
The 2007 International Scientific Conference of Options for the Control of Influenza (Options-6), Toronto, ON., Canada, 17-23 June 2007. In Conference Proceedings, 2007, p. 545 How to Cite?
AbstractINTRODUCTION: Highly pathogenic avian influenza virus (H5N1) is the first avian influenza virus that documented to cause respiratory disease and death in human. The biological basis for the severe human disease and high fatality rate remains unclear. We have previously demonstrated that when compared to human H1N1 and H3N2 influenza viruses, infection of influenza H5N1 virus led to the hyper-induction of pro-inflammatory cytokines in human primary macrophages and non-polarized respiratory epithelial cells in vitro. We also reported that patients with H5N1 disease have unusually high serum concentration of chemokines, e.g., IP-10. We therefore hypothesized that the differential hyper-induction of pro-inflammatory cytokines may contribute to the unusual severity of human H5N1 disease. In human, pathology of influenza A (H5N1) viruses are primarily respiratory pathogens targeting the respiratory epithelium, resulting in high level of cell death and tissue damage. As respiratory epithelial cells are primary target cells for replication of influenza viruses, a full understanding of how influenza virus interacts with respiratory epithelium is vital to advance our knowledge of its tropism and pathogenesis. METHODS: Primary human respiratory (bronchial and alveolar) epithelial cells were isolated and seeded onto collagen-coated transwell filters and cultured under air-liquid interface until cells were polarized and differentiated. The replication kinetic of influenza virus was assessed by virus yield titration (TCID50) in MDCK cells. The cytokines expression profile induced by influenza H5N1 viruses (A/HK/483/97 and A/Vietnam/3046/04) was compared with human H1N1 virus by quantitative RT-PCR and ELISA. RESULTS: Polarized and differentiated bronchial and alveolar epithelial cells models are established for the study (Figure 1). We demonstrated that influenza A viruses (H5N1 and H1N1) can infect and productively replicate in the bronchial and alveolar epithelial cells leading to cytopathic effects. We found that the respiratory epithelial cells infected on the apical rather than the basolateral surface showed high levels of viral replication. Progeny influenza virus was released into the apical chamber at titers up to 3 logs higher than those recovered from the basolateral surface of polarized cell cultures (Figure 2). Influenza H5N1 viruses were more potent inducers of cytokines in human respiratory epithelial cells when compared to the H1N1 virus. We show that these cytokines are released preferentially at the basolateral aspect of the polarized epithelial cells (Figure 3). CONCLUSION: Our data suggest that influenza H5N1 viruses enter and are released from the apical domain of respiratory epithelium, while the pro-inflammatory cytokines are released preferentially from the basolateral aspect of the respiratory epithelium. These finding may provide important insights into the mechanism of replication and pathogenesis of influenza H5N1 virus in humans.
DescriptionPoster Presentations: Virus Host Interaction/Pathogenesis
Persistent Identifierhttp://hdl.handle.net/10722/103085
ISBN

 

DC FieldValueLanguage
dc.contributor.authorChan, MCWen_HK
dc.contributor.authorChan, RWYen_HK
dc.contributor.authorYu, CLen_HK
dc.contributor.authorNicholls, JMen_HK
dc.contributor.authorChui, WHen_HK
dc.contributor.authorGuan, Yen_HK
dc.contributor.authorPeiris, JSMen_HK
dc.date.accessioned2010-09-25T20:57:20Z-
dc.date.available2010-09-25T20:57:20Z-
dc.date.issued2007en_HK
dc.identifier.citationThe 2007 International Scientific Conference of Options for the Control of Influenza (Options-6), Toronto, ON., Canada, 17-23 June 2007. In Conference Proceedings, 2007, p. 545-
dc.identifier.isbn978-1-901-769-15-6-
dc.identifier.urihttp://hdl.handle.net/10722/103085-
dc.descriptionPoster Presentations: Virus Host Interaction/Pathogenesis-
dc.description.abstractINTRODUCTION: Highly pathogenic avian influenza virus (H5N1) is the first avian influenza virus that documented to cause respiratory disease and death in human. The biological basis for the severe human disease and high fatality rate remains unclear. We have previously demonstrated that when compared to human H1N1 and H3N2 influenza viruses, infection of influenza H5N1 virus led to the hyper-induction of pro-inflammatory cytokines in human primary macrophages and non-polarized respiratory epithelial cells in vitro. We also reported that patients with H5N1 disease have unusually high serum concentration of chemokines, e.g., IP-10. We therefore hypothesized that the differential hyper-induction of pro-inflammatory cytokines may contribute to the unusual severity of human H5N1 disease. In human, pathology of influenza A (H5N1) viruses are primarily respiratory pathogens targeting the respiratory epithelium, resulting in high level of cell death and tissue damage. As respiratory epithelial cells are primary target cells for replication of influenza viruses, a full understanding of how influenza virus interacts with respiratory epithelium is vital to advance our knowledge of its tropism and pathogenesis. METHODS: Primary human respiratory (bronchial and alveolar) epithelial cells were isolated and seeded onto collagen-coated transwell filters and cultured under air-liquid interface until cells were polarized and differentiated. The replication kinetic of influenza virus was assessed by virus yield titration (TCID50) in MDCK cells. The cytokines expression profile induced by influenza H5N1 viruses (A/HK/483/97 and A/Vietnam/3046/04) was compared with human H1N1 virus by quantitative RT-PCR and ELISA. RESULTS: Polarized and differentiated bronchial and alveolar epithelial cells models are established for the study (Figure 1). We demonstrated that influenza A viruses (H5N1 and H1N1) can infect and productively replicate in the bronchial and alveolar epithelial cells leading to cytopathic effects. We found that the respiratory epithelial cells infected on the apical rather than the basolateral surface showed high levels of viral replication. Progeny influenza virus was released into the apical chamber at titers up to 3 logs higher than those recovered from the basolateral surface of polarized cell cultures (Figure 2). Influenza H5N1 viruses were more potent inducers of cytokines in human respiratory epithelial cells when compared to the H1N1 virus. We show that these cytokines are released preferentially at the basolateral aspect of the polarized epithelial cells (Figure 3). CONCLUSION: Our data suggest that influenza H5N1 viruses enter and are released from the apical domain of respiratory epithelium, while the pro-inflammatory cytokines are released preferentially from the basolateral aspect of the respiratory epithelium. These finding may provide important insights into the mechanism of replication and pathogenesis of influenza H5N1 virus in humans.-
dc.languageengen_HK
dc.publisherInternational Medical Press Ltd.-
dc.relation.ispartofInternational Scientific Conference of Options for the Control of Influenza, Options-6en_HK
dc.titlePolarity of influenza H5N1 virus infection in respiratory epithelial cells and the impact of basolateral release of cytokines in disease pathogenesisen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailChan, MCW: mchan@hku.hken_HK
dc.identifier.emailChan, WY: reneechan@graduate.hku.hken_HK
dc.identifier.emailHo, CC: chui2ho@hku.hken_HK
dc.identifier.emailNicholls, JM: nicholls@pathology.hku.hken_HK
dc.identifier.emailCheung, CY: chungey@hkucc.hku.hken_HK
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hken_HK
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hken_HK
dc.identifier.authorityChan, MCW=rp00420en_HK
dc.identifier.authorityNicholls, JM=rp00364en_HK
dc.identifier.authorityCheung, CY=rp00404en_HK
dc.identifier.authorityGuan, Y=rp00397en_HK
dc.identifier.authorityPeiris, JSM=rp00410en_HK
dc.identifier.hkuros132632en_HK
dc.identifier.spage545-
dc.identifier.epage545-
dc.publisher.placeUnited States-

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