Multiple Respiratory Syncytial Virus (RSV) Strains Infecting HEp-2 and A549 Cells Reveal Cell Line-Dependent Differences in Resistance to RSV Infection.

TitleMultiple Respiratory Syncytial Virus (RSV) Strains Infecting HEp-2 and A549 Cells Reveal Cell Line-Dependent Differences in Resistance to RSV Infection.
Publication TypeJournal Article
Year of Publication2022
AuthorsRajan, A, Piedra, F-A, Aideyan, L, McBride, T, Robertson, M, Johnson, HL, Aloisio, GMarie, Henke, D, Coarfa, C, Stossi, F, Menon, VKumar, Doddapaneni, H, Muzny, DMarie, Cregeen, SJoan Javor, Hoffman, KLouise, Petrosino, J, Gibbs, RA, Avadhanula, V, Piedra, PA
JournalJ Virol
Date Published2022 Apr 13
KeywordsA549 Cells, Antiviral Agents, Cell Line, Host Microbial Interactions, Humans, Respiratory Syncytial Virus Infections, Respiratory Syncytial Virus, Human, Severity of Illness Index, Species Specificity, Virus Replication

Respiratory syncytial virus (RSV) is a leading cause of pediatric acute respiratory infection worldwide. There are currently no approved vaccines or antivirals to combat RSV disease. A few transformed cell lines and two historic strains have been extensively used to study RSV. Here, we reported a thorough molecular and cell biological characterization of HEp-2 and A549 cells infected with one of four strains of RSV representing both major subgroups as well as historic and more contemporary genotypes (RSV/A/Tracy [GA1], RSV/A/Ontario [ON], RSV/B/18537 [GB1], and RSV/B/Buenos Aires [BA]) via measurements of viral replication kinetics and viral gene expression, immunofluorescence-based imaging of gross cellular morphology and cell-associated RSV, and measurements of host response, including transcriptional changes and levels of secreted cytokines and growth factors. Infection with the respiratory syncytial virus (RSV) early in life is essentially guaranteed and can lead to severe disease. Most RSV studies have involved either of two historic RSV/A strains infecting one of two cell lines, HEp-2 or A549 cells. However, RSV contains ample variation within two evolving subgroups (A and B), and HEp-2 and A549 cell lines are genetically distinct. Here, we measured viral action and host response in both HEp-2 and A549 cells infected with four RSV strains from both subgroups and representing both historic and more contemporary strains. We discovered a subgroup-dependent difference in viral gene expression and found A549 cells were more potently antiviral and more sensitive, albeit subtly, to viral variation. Our findings revealed important differences between RSV subgroups and two widely used cell lines and provided baseline data for experiments with model systems better representative of natural RSV infection.

Alternate JournalJ Virol
PubMed ID35285685
PubMed Central IDPMC9006923
Grant ListU19 AI144297 / AI / NIAID NIH HHS / United States
P30 ES030285 / ES / NIEHS NIH HHS / United States
P30 CA125123 / CA / NCI NIH HHS / United States
T32 AI055413 / AI / NIAID NIH HHS / United States
P30 DK056338 / DK / NIDDK NIH HHS / United States