Article: H5N1 influenza virus-induced mediators upregulate RIG-I in uninfected cells by paracrine effects contributing to amplified cytokine cascades
| Title | H5N1 influenza virus-induced mediators upregulate RIG-I in uninfected cells by paracrine effects contributing to amplified cytokine cascades | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Hui, KPY1 Lee, SMY1 Cheung, CY1 Mao, H1 Lai, AKW1 Chan, RWY1 Chan, MCW1 Tu, W1 Guan, Y1 Lau, YL1 Peiris, JSM1 2 | ||||||
| Issue Date | 2011 | ||||||
| Publisher | Oxford University Press. The Journal's web site is located at http://jid.oxfordjournals.org | ||||||
| Citation | Journal Of Infectious Diseases, 2011, v. 204 n. 12, p. 1866-1878 [How to Cite?] DOI: http://dx.doi.org/10.1093/infdis/jir665 | ||||||
| Abstract | Highly pathogenic avian influenza H5N1 viruses cause severe disease in humans, and dysregulation of cytokine responses is believed to contribute to the pathogenesis of human H5N1 disease. However, mechanisms leading to the increased induction of proinflammatory cytokines by H5N1 viruses are poorly understood. We show that the innate sensing receptor RIG-I is involved in interferon regulatory factor 3 (IRF3), NF-κB nuclear translocation, p38 activation, and the subsequent interferon (IFN) β, IFN-λ1, and tumor necrosis factor α induction during H5N1 infection. Soluble mediators from H5N1-infected human macrophages upregulate RIG-I, MDA5, and TLR3 to much higher levels than those from seasonal H1N1 in uninfected human macrophages and alveolar epithelial cells via paracrine IFNAR1/JAK but not IFN-λ receptor signaling. Compared with H1N1 virus-induced mediators, H5N1 mediators markedly enhance the cytokine response to PolyIC and to both seasonal and H5N1 virus infection in a RIG-I-dependent manner. Thus, sensitizing neighboring cells by upregulation of RIG-I contributes to the amplified cytokine cascades during H5N1 infection. © 2011 The Author. | ||||||
| ISSN | 0022-1899 2011 Impact Factor: 6.41 2011 SCImago Journal Rankings: 0.831 | ||||||
| DOI | http://dx.doi.org/10.1093/infdis/jir665 | ||||||
| ISI Accession Number ID | WOS:000297069100009
Funding Information: This work was supported by an RFCID grant (10091062) from the Food and Health Bureau of Hong Kong SAR and a grant from the Research Grant Council of Hong Kong SAR (7620/06M). | ||||||
| References | References in Scopus | ||||||
| Grants | Role of retinoic acid inducible gene-1, toll-like receptor-3 and -8 in cytokine induction by influenza A H5N1 and pandemic H1N1 viruses in primary human cells |
| dc.contributor.author | Hui, KPY | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Lee, SMY | ||||||
| dc.contributor.author | Cheung, CY | ||||||
| dc.contributor.author | Mao, H | ||||||
| dc.contributor.author | Lai, AKW | ||||||
| dc.contributor.author | Chan, RWY | ||||||
| dc.contributor.author | Chan, MCW | ||||||
| dc.contributor.author | Tu, W | ||||||
| dc.contributor.author | Guan, Y | ||||||
| dc.contributor.author | Lau, YL | ||||||
| dc.contributor.author | Peiris, JSM | ||||||
| dc.date.accessioned | 2012-04-20T02:05:13Z | ||||||
| dc.date.available | 2012-04-20T02:05:13Z | ||||||
| dc.date.issued | 2011 | ||||||
| dc.description.abstract | Highly pathogenic avian influenza H5N1 viruses cause severe disease in humans, and dysregulation of cytokine responses is believed to contribute to the pathogenesis of human H5N1 disease. However, mechanisms leading to the increased induction of proinflammatory cytokines by H5N1 viruses are poorly understood. We show that the innate sensing receptor RIG-I is involved in interferon regulatory factor 3 (IRF3), NF-κB nuclear translocation, p38 activation, and the subsequent interferon (IFN) β, IFN-λ1, and tumor necrosis factor α induction during H5N1 infection. Soluble mediators from H5N1-infected human macrophages upregulate RIG-I, MDA5, and TLR3 to much higher levels than those from seasonal H1N1 in uninfected human macrophages and alveolar epithelial cells via paracrine IFNAR1/JAK but not IFN-λ receptor signaling. Compared with H1N1 virus-induced mediators, H5N1 mediators markedly enhance the cytokine response to PolyIC and to both seasonal and H5N1 virus infection in a RIG-I-dependent manner. Thus, sensitizing neighboring cells by upregulation of RIG-I contributes to the amplified cytokine cascades during H5N1 infection. © 2011 The Author. | ||||||
| dc.description.grant | Role of retinoic acid inducible gene-1, toll-like receptor-3 and -8 in cytokine induction by influenza A H5N1 and pandemic H1N1 viruses in primary human cells | ||||||
| dc.description.grantcode | 103771 | ||||||
| dc.description.nature | Link_to_OA_fulltext | ||||||
| dc.identifier.citation | Journal Of Infectious Diseases, 2011, v. 204 n. 12, p. 1866-1878 [How to Cite?] DOI: http://dx.doi.org/10.1093/infdis/jir665 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1093/infdis/jir665 | ||||||
| dc.identifier.epage | 1878 | ||||||
| dc.identifier.hkuros | 200729 | ||||||
| dc.identifier.hkuros | 202477 | ||||||
| dc.identifier.isi | WOS:000297069100009
Funding Information: This work was supported by an RFCID grant (10091062) from the Food and Health Bureau of Hong Kong SAR and a grant from the Research Grant Council of Hong Kong SAR (7620/06M). | ||||||
| dc.identifier.issn | 0022-1899 2011 Impact Factor: 6.41 2011 SCImago Journal Rankings: 0.831 | ||||||
| dc.identifier.issue | 12 | ||||||
| dc.identifier.pmid | 22013225 | ||||||
| dc.identifier.scopus | eid_2-s2.0-81055143878 | ||||||
| dc.identifier.spage | 1866 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/146347 | ||||||
| dc.identifier.volume | 204 | ||||||
| dc.language | eng | ||||||
| dc.publisher | Oxford University Press. The Journal's web site is located at http://jid.oxfordjournals.org | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | Journal of Infectious Diseases | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.subject.mesh | Adaptor Proteins, Signal Transducing - genetics - immunology - metabolism | ||||||
| dc.subject.mesh | Cells, Cultured | ||||||
| dc.subject.mesh | Cytokines - metabolism | ||||||
| dc.subject.mesh | DEAD-box RNA Helicases - genetics - immunology - metabolism | ||||||
| dc.subject.mesh | Epithelial Cells - immunology - metabolism | ||||||
| dc.subject.mesh | Humans | ||||||
| dc.subject.mesh | Immunity, Innate | ||||||
| dc.subject.mesh | Influenza A Virus, H1N1 Subtype - genetics - immunology | ||||||
| dc.subject.mesh | Influenza A Virus, H5N1 Subtype - genetics - immunology | ||||||
| dc.subject.mesh | Influenza, Human - immunology - metabolism - virology | ||||||
| dc.subject.mesh | Interferon Regulatory Factor-3 - metabolism | ||||||
| dc.subject.mesh | Janus Kinases - immunology | ||||||
| dc.subject.mesh | Macrophages - immunology - metabolism | ||||||
| dc.subject.mesh | NF-kappa B - metabolism | ||||||
| dc.subject.mesh | Paracrine Communication - immunology | ||||||
| dc.subject.mesh | Pulmonary Alveoli - immunology - metabolism | ||||||
| dc.subject.mesh | RNA, Small Interfering - genetics | ||||||
| dc.subject.mesh | RNA, Viral - metabolism | ||||||
| dc.subject.mesh | Receptor, Interferon alpha-beta - immunology | ||||||
| dc.subject.mesh | Signal Transduction | ||||||
| dc.subject.mesh | Toll-Like Receptor 3 - metabolism | ||||||
| dc.subject.mesh | Up-Regulation | ||||||
| dc.subject.mesh | p38 Mitogen-Activated Protein Kinases - metabolism | ||||||
| dc.title | H5N1 influenza virus-induced mediators upregulate RIG-I in uninfected cells by paracrine effects contributing to amplified cytokine cascades | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong Li Ka Shing Faculty of Medicine
- HKU-Pasteur Research Centre