Host regulatory network response to infection with highly pathogenic H5N1 avian influenza virus

Chengjun Li, Armand Bankhead, Amie J. Eisfeld, Yasuko Hatta, Sophia Jeng, Jean H. Chang, Lauri D. Aicher, Sean Proll, Amy L. Ellis, G. Lynn Law, Katrina M. Waters, Gabriele Neumann, Michael G. Katze, Shannon McWeeney, Yoshihiro Kawaoka

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


During the last decade, more than half of humans infected with highly pathogenic avian influenza (HPAI) H5N1 viruses have died, yet virus-induced host signaling has yet to be clearly elucidated. Airway epithelia are known to produce inflammatory mediators that contribute to HPAI H5N1-mediated pathogenicity, but a comprehensive analysis of the host response in this cell type is lacking. Here, we leveraged a system approach to identify and statistically validate signaling subnetworks that define the dynamic transcriptional response of human bronchial epithelial cells after infection with influenza A/Vietnam/1203/2004 (H5N1, VN1203). Importantly, we validated a subset of transcripts from one subnetwork in both Calu-3 cells and mice. A more detailed examination of two subnetworks involved in the immune response and keratinization processes revealed potential novel mediators of HPAI H5N1 pathogenesis and host response signaling. Finally, we show how these results compare to those for a less virulent strain of influenza virus. Using emergent network properties, we provide fresh insight into the host response to HPAI H5N1 virus infection and identify novel avenues for perturbation studies and potential therapeutic interventions for fatal HPAI H5N1 disease.

Original languageEnglish (US)
Pages (from-to)10955-10967
Number of pages13
JournalJournal of virology
Issue number21
StatePublished - Nov 2011

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology


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