Differential Responses by Human Respiratory Epithelial Cell Lines to Respiratory Syncytial Virus Reflect Distinct Patterns of Infection Control

Abstract

Respiratory syncytial virus (RSV) infects small foci of respiratory epithelial cells via infected droplets. Infection induces expression of type I and III interferons (IFNs) and proinflammatory 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-β-, IFN-λ-, and NF-κB-inducible proinflammatory cytokines. In contrast, BEAS-2B cells expressed higher levels of antiviral interferon-stimulated genes, pattern recognition receptors, and other signaling intermediaries constitutively and after infection. Transcriptome analysis revealed that constitutive expression of antiviral and proinflammatory 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. Airway epithelium is both the primary target of 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 responses. 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 proinflammatory response. In contrast, BEAS-2B cells restrict infection and express genes characteristic of an antiviral response associated with expression of type 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 for identifying critical mediators of local control of infection and stresses the importance of the constitutive antiviral state for the response to viral challenge.

Comparative Transcriptomic Analysis of Rhinovirus and Influenza Virus Infection

“…Host gene response after RV infection has been previously compared to that of influenza virus infection in a human bronchial epithelial cell line BEAS-2B cells using microarray analysis (Kim et al, 2015). However, BEAS-2B has high basal production of interferon-stimulated genes which may affect the response of other host genes (Seng et al, 2014;Hillyer et al, 2018). In this study, we compared the host response between influenza virus and RV in a well-characterized lower airway cell line, Calu-3, using RNA-seq.…”

Metatranscriptomic Characterization of Coronavirus Disease 2019 Identified a Host Transcriptional Classifier Associated With Immune Signaling

“…For instance, the interferon pathway was significantly enriched in the COVID-19 cases in the NS group, which might reflect the viral responses of epithelial cells [41,42]. Enrichment of the interleukin pathway was found in the SP samples, which might indicate viral responses of immune cells [43,44].…”

Metabolic changes during respiratory syncytial virus infection of epithelial cells

“…Transcriptomic and proteomic studies have shown the profound impact of HRSV on the physiology of respiratory epithelial cells, its main targets for infection. However, most of those studies have focused on the early innate immune response elicited in the infected cells [12][13][14]. Although, changes in other aspects of the virus-host cell interactions have also been reported, including those involving cell growth, cytoskeleton organization and mitochondrial electron transport [15][16][17][18].…”