Early Host Responses of Seasonal and Pandemic Influenza A Viruses in Primary Well-Differentiated Human Lung Epithelial Cells

CCL5
DOI: 10.1371/journal.pone.0078912 Publication Date: 2013-11-14T22:53:17Z
ABSTRACT
Replication, cell tropism and the magnitude of host's antiviral immune response each contribute to resulting pathogenicity influenza A viruses (IAV) in humans. In contrast seasonal IAV human cases, 2009 H1N1 pandemic (H1N1pdm) shows a greater for infection lung similar H5N1. We hypothesized that host responses during well-differentiated, primary bronchial epithelial cells (wd-NHBE) may differ between (H1N1 A/BN/59/07) H1N1pdm isolates from fatal (A/KY/180/10) nonfatal (A/KY/136/09) case. For virus, level infectious virus (gene expression apical/basal cytokine/chemokine profiles) were measured wd-NHBE at 8, 24, 36, 48 72 hours post-infection (hpi). At 24 36 hpi, KY/180 showed significant, ten-fold higher titer as compared other two isolates. Apical levels IL-6, IL-8 GRO infected by these viruses. NHBE had pro-inflammatory cytokines including IFN-α, CCL2, TNF-α, CCL5, when with seasonal. Polarization IL-6 was greatest hpi all Differential polarized secretion suggested CCL5 across Despite differences viral isolates, no significant observed KY/136 gene intensity profiles. Microarray profiles diverged 1647 genes commonly shared pandemic, but not Significant cytokine signaling, apoptosis, cytoskeletal arrangement pathways. Our studies revealed temporal dynamics basal isolate; however, significantly different suggesting post-transcriptional or later viral-host interactions.
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