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

Tomoki Yoshikawa, Terence E. Hill, Naoko Yoshikawa, Vsevolod Popov, Cristi L. Galindo, Harold R. Garner, C. J. Peters, Chien-Te Tseng

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Human lung epithelial cells are likely among the first targets to encounter invading severe acute respiratory syndrome-associated 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 microarray-based 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)κB, 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)-β, -λs, inflammatory mediators, and many IFN-stimulated genes (ISGs). We also showed, for the first time, that IFN-β and IFN-λs 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.

Original languageEnglish (US)
Article numbere8729
JournalPLoS One
Volume5
Issue number1
DOIs
StatePublished - Jan 15 2010

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Coronavirus Infections
Severe Acute Respiratory Syndrome
Coronavirinae
Coronavirus
Innate Immunity
Interferons
interferons
epithelial cells
Epithelial Cells
Genes
infection
Antiviral Agents
Chemical activation
Interferon Regulatory Factor-3
Interferon Regulatory Factor-7
lungs
cells
Transcription Factor AP-1
Pathology
Microarrays

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Dynamic innate immune responses of human bronchial epithelial cells to severe acute respiratory syndrome-associated coronavirus infection. / Yoshikawa, Tomoki; Hill, Terence E.; Yoshikawa, Naoko; Popov, Vsevolod; Galindo, Cristi L.; Garner, Harold R.; Peters, C. J.; Tseng, Chien-Te.

In: PLoS One, Vol. 5, No. 1, e8729, 15.01.2010.

Research output: Contribution to journalArticle

Yoshikawa, Tomoki ; Hill, Terence E. ; Yoshikawa, Naoko ; Popov, Vsevolod ; Galindo, Cristi L. ; Garner, Harold R. ; Peters, C. J. ; Tseng, Chien-Te. / Dynamic innate immune responses of human bronchial epithelial cells to severe acute respiratory syndrome-associated coronavirus infection. In: PLoS One. 2010 ; Vol. 5, No. 1.
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