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

Author:

Hillyer Philippa1ORCID,Shepard Rachel1,Uehling Megan1,Krenz Mina1,Sheikh Faruk2,Thayer Kalyn R.1,Huang Lei3,Yan Lihan3,Panda Debasis1,Luongo Cindy4,Buchholz Ursula J.4,Collins Peter L.4,Donnelly Raymond P.2ORCID,Rabin Ronald L.1ORCID

Affiliation:

1. Laboratory of Immunobiochemistry, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA

2. Division of Biotechnology Research and Review 2, Office of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA

3. Division of Biostatistics, Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA

4. Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

Abstract

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.

Funder

HHS | National Institutes of Health

HHS | U.S. Food and Drug Administration

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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