Early host responses of seasonal and pandemic influenza a viruses in primary well-differentiated human lung epithelial cells

Rachael L. Gerlach, Jeremy V. Camp, Yong Kyu Chu, Colleen Jonsson

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Replication, cell tropism and the magnitude of the host's antiviral immune response each contribute to the resulting pathogenicity of influenza A viruses (IAV) in humans. In contrast to seasonal IAV in human cases, the 2009 H1N1 pandemic IAV (H1N1pdm) shows a greater tropism for infection of the lung similar to H5N1. We hypothesized that host responses during infection of well-differentiated, primary human bronchial epithelial cells (wd-NHBE) may differ between seasonal (H1N1 A/BN/59/07) and H1N1pdm isolates from a fatal (A/KY/180/10) and nonfatal (A/KY/136/09) case. For each virus, the level of infectious virus and host response to infection (gene expression and apical/basal cytokine/chemokine profiles) were measured in wd-NHBE at 8, 24, 36, 48 and 72 hours post-infection (hpi). At 24 and 36 hpi, KY/180 showed a significant, ten-fold higher titer as compared to the other two isolates. Apical cytokine/chemokine levels of IL-6, IL-8 and GRO were similar in wd-NHBE cells infected by each of these viruses. At 24 and 36 hpi, NHBE cells had greater levels of pro-inflammatory cytokines including IFN-α, CCL2, TNF-α, and CCL5, when infected by pandemic viruses as compared with seasonal. Polarization of IL-6 in wd-NHBE cells was greatest at 36 hpi for all isolates. Differential polarized secretion was suggested for CCL5 across isolates. Despite differences in viral titer across isolates, no significant differences were observed in KY/180 and KY/136 gene expression intensity profiles. Microarray profiles of wd-NHBE cells diverged at 36 hpi with 1647 genes commonly shared by wd-NHBE cells infected by pandemic, but not seasonal isolates. Significant differences were observed in cytokine signaling, apoptosis, and cytoskeletal arrangement pathways. Our studies revealed differences in temporal dynamics and basal levels of cytokine/chemokine responses of wd-NHBE cells infected with each isolate; however, wd-NHBE cell gene intensity profiles were not significantly different between the two pandemic isolates suggesting post-transcriptional or later differences in viral-host interactions.

Original languageEnglish (US)
Article numbere78912
JournalPloS one
Volume8
Issue number11
DOIs
StatePublished - Nov 14 2013

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Pandemics
pandemic
Orthomyxoviridae
Viruses
epithelial cells
Epithelial Cells
lungs
Lung
Cytokines
Infection
cytokines
infection
Chemokines
Influenza A virus
chemokines
cells
viruses
tropisms
Gene expression
Interleukin-6

All Science Journal Classification (ASJC) codes

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

Cite this

Early host responses of seasonal and pandemic influenza a viruses in primary well-differentiated human lung epithelial cells. / Gerlach, Rachael L.; Camp, Jeremy V.; Chu, Yong Kyu; Jonsson, Colleen.

In: PloS one, Vol. 8, No. 11, e78912, 14.11.2013.

Research output: Contribution to journalArticle

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