Dynamic innate immune responses of human bronchial epithelial cells to severe acute respiratory syndrome-associated coronavirus infection

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dc.contributor.authorYoshikawa, Tomokien
dc.contributor.authorHill, Terence E.en
dc.contributor.authorYoshikawa, Naokoen
dc.contributor.authorPopov, Vsevolod L.en
dc.contributor.authorGalindo, Cristi L.en
dc.contributor.authorGarner, Harold R.en
dc.contributor.authorPeters, C. J.en
dc.contributor.authorTseng, Chien-Te (Kent)en
dc.date.accessed2014-05-14en
dc.date.accessioned2014-06-17T20:12:04Zen
dc.date.available2014-06-17T20:12:04Zen
dc.date.issued2010-01-15en
dc.description.abstractHuman lung epithelial cells are likely among the first targets to encounter invading severe acute respiratory syndromeassociated coronavirus (SARS-CoV). Not only can these cells support the growth of SARS-CoV infection, but they are also capable of secreting inflammatory cytokines to initiate and, eventually, aggravate host innate inflammatory responses, causing detrimental immune-mediated pathology within the lungs. Thus, a comprehensive evaluation of the complex epithelial signaling to SARS-CoV is crucial for paving the way to better understand SARS pathogenesis. Based on microarraybased functional genomics, we report here the global gene response of 2B4 cells, a cloned bronchial epithelial cell line derived from Calu-3 cells. Specifically, we found a temporal and spatial activation of nuclear factor (NF)kB, activator protein (AP)-1, and interferon regulatory factor (IRF)-3/7 in infected 2B4 cells at 12-, 24-, and 48-hrs post infection (p.i.), resulting in the activation of many antiviral genes, including interferon (IFN)-b, -ls, inflammatory mediators, and many IFN-stimulated genes (ISGs). We also showed, for the first time, that IFN-b and IFN-ls were capable of exerting previously unrecognized, non-redundant, and complementary abilities to limit SARS-CoV replication, even though their expression could not be detected in infected 2B4 bronchial epithelial cells until 48 hrs p.i. Collectively, our results highlight the mechanics of the sequential events of antiviral signaling pathway/s triggered by SARS-CoV in bronchial epithelial cells and identify novel cellular targets for future studies, aiming at advancing strategies against SARS.en
dc.description.sponsorshipThis work was supported by National Institutes of Health (http://www3.niaid.nih.gov/) Grant R21AI072201, a Career Development Grant award through the Western Regional Center of Excellence for Biodefense and Emerging Infectious Diseases (U54 AI057156), as well as Subcontract awards on SARS from the Viral Respiratory Pathogens Research Unit (NO1 AI3009) (to CKT), and US Based Collaboration in Emerging Viral and Prior Diseases (NO1 AI25489). T.Y. was supported by the James W. McLaughlin Fellowship Fund (http://research.utmb.edu/intramural_funding/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.identifier.citationYoshikawa T, Hill TE, Yoshikawa N, Popov VL, Galindo CL, et al. (2010) Dynamic Innate Immune Responses of Human Bronchial Epithelial Cells to Severe Acute Respiratory Syndrome-Associated Coronavirus Infection. PLoS ONE 5(1): e8729. doi:10.1371/journal.pone.0008729en
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0008729en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://hdl.handle.net/10919/48976en
dc.identifier.urlhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008729en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectAntiviralsen
dc.subjectDNA transcriptionen
dc.subjectGene expressionen
dc.subjectImmune responseen
dc.subjectInflammationen
dc.subjectRespiratory infectionsen
dc.subjectSARSen
dc.subjectVirus effects on host gene expressionen
dc.titleDynamic innate immune responses of human bronchial epithelial cells to severe acute respiratory syndrome-associated coronavirus infectionen
dc.title.serialPLoS ONEen
dc.typeArticle - Refereeden

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