Host immune and apoptotic responses to avian influenza virus H9N2 in human tracheobronchial epithelial cells

Zheng Xing, Richart W Harper, Jerome Anunciacion, Zengqi Yang, Wei Gao, Bingqian Qu, Yi Guan, Carol J. Cardona

Research output: Contribution to journalArticle

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Abstract

The avian influenza virus H9N2 subtype has circulated in wild birds, is prevalent in domestic poultry, and has successfully crossed the species boundary to infect humans. Phylogenetic analyses showed that viruses of this subtype appear to have contributed to the generation of highly pathogenic H5N1 viruses. Little is known about the host responses to H9N2 viruses in human airway respiratory epithelium, the primary portal for viral infection. Using an apically differentiated primary human tracheobronchial epithelial (TBE) culture, we examined host immune responses to infection by an avian H9N2 virus, in comparison with a human H9N2 isolate. We found that IFN-β was the prominent antiviral component, whereas interferon gamma-induced protein 10 kDa (IP-10), chemokine (C-C motif) ligand (CCL)-5 and TNF-α may be critical in proinflammatory responses to H9N2 viruses. In contrast, proinflammatory IL-1β, IL-8, and even IL-6 may only play a minor role in pathogenicity. Apparently Toll-like receptor (TLR)-3, TLR-7, and melanoma differentiation- associated gene 5 (MDA-5) contributed to the innate immunity against theH9N2viruses, andMDA-5was important in the induction of IFN-β. We showed that the avian H9N2 virus induced apoptosis through the mitochondria/cytochrome c-mediated intrinsic pathway, in addition to the caspase 8-mediated extrinsic pathway, as evidenced by the cytosolic presence of active caspase 9 and cytochrome c, independent of truncated BH3 interacting domain death agonist (Bid) activation. Further, we demonstrated that FLICE-like inhibitory protein (FLIP), an apoptotic dual regulator, and the p53- dependent Bcl-2 family members, Bax and Bcl-xs, appeared to be involved in the regulation of extrinsic and intrinsic apoptotic pathways, respectively. The findings in this study will further our understanding of host defense mechanisms and the pathogenesis of H9N2 influenza viruses in human respiratory epithelium.

Original languageEnglish (US)
Pages (from-to)24-33
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume44
Issue number1
DOIs
StatePublished - Jan 1 2010

Fingerprint

H9N2 Subtype Influenza A Virus
Influenza in Birds
Orthomyxoviridae
Viruses
Epithelial Cells
Respiratory Mucosa
Cytochromes c
CASP8 and FADD-Like Apoptosis Regulating Protein
Toll-Like Receptor 7
Toll-Like Receptor 3
H5N1 Subtype Influenza A Virus
CC Chemokines
Caspase 9
Caspase 8
Virus Diseases
Defense Mechanisms
Poultry
Interleukin-8
Interleukin-1
Innate Immunity

Keywords

  • Apoptosis
  • Avian influenza virus
  • Bronchial epithelial cells
  • Chemokines
  • Cytokines
  • H9N2
  • Host responses

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Host immune and apoptotic responses to avian influenza virus H9N2 in human tracheobronchial epithelial cells. / Xing, Zheng; Harper, Richart W; Anunciacion, Jerome; Yang, Zengqi; Gao, Wei; Qu, Bingqian; Guan, Yi; Cardona, Carol J.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 44, No. 1, 01.01.2010, p. 24-33.

Research output: Contribution to journalArticle

Xing, Zheng ; Harper, Richart W ; Anunciacion, Jerome ; Yang, Zengqi ; Gao, Wei ; Qu, Bingqian ; Guan, Yi ; Cardona, Carol J. / Host immune and apoptotic responses to avian influenza virus H9N2 in human tracheobronchial epithelial cells. In: American Journal of Respiratory Cell and Molecular Biology. 2010 ; Vol. 44, No. 1. pp. 24-33.
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AU - Guan, Yi

AU - Cardona, Carol J.

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