Scientific Publications by FDA Staff

J Virol 2018 Jul 17;92(15):e02202-17

Differential responses by human respiratory epithelial cell lines to respiratory syncytial virus reflect distinct patterns of infection control.

Hillyer P, Shepard R, Uehling M, Krenz M, Sheikh F, Thayer KR, Huang L, Yan L, Panda D, Luongo C, Buchholz UJ, Collins PL, Donnelly RP, Rabin RL

RSV infects small foci of respiratory epithelial cells via infected droplets. Infection induces expression of types I and III interferons (IFNs) and pro-inflammatory cytokines, the balance of which may restrict viral replication and affect disease severity. We explored this balance by infecting two respiratory epithelial cell lines with low doses of recombinant RSV expressing green fluorescent protein (rgRSV). A549 cells were highly permissive whereas BEAS-2B cells restricted infection to individual cells or small foci. After infection, A549 cells expressed higher levels of IFN-beta, IFN-lambda, and NF-kappaB inducible pro-inflammatory cytokines. In contrast, BEAS-2B cells expressed higher levels of anti-viral interferon-stimulated genes, pattern recognition receptors, and other signaling intermediaries constitutively and after infection. Transcriptome analysis revealed that constitutive expression of antiviral and pro-inflammatory genes predicted responses by each cell line. These two cell lines provide a model for elucidating critical mediators of local control of viral infection in respiratory epithelial cells. IMPORTANCE: Airway epithelium is both the primary target and the first defense against respiratory syncytial virus (RSV). Whether RSV replicates and spreads to adjacent epithelial cells depends on the quality of their innate immune response. A549 and BEAS-2B are alveolar and bronchial epithelial cell lines, respectively, that are often used to study RSV infection. We show that A549 cells are permissive to RSV infection and express genes characteristic of a pro-inflammatory response. By contrast, BEAS-2B cells restrict infection and express genes characteristic of an antiviral response associated with expression of types I and III interferons. Transcriptome analysis of constitutive gene expression revealed patterns that may predict the response of each cell line to infection. This study suggests that restrictive and permissive cell lines may provide a model towards identifying critical mediators of local control of infection, and stresses the importance of the constitutive antiviral state towards the response to viral challenge.