Differential cytopathogenesis of respiratory syncytial virus prototypic and clinical isolates in primary pediatric bronchial epithelial cells

Rémi Villenave,Surendran Thavagnanam,Olivier Touzelet,James P Mckaigue,Ultan F Power,Grzegorz Skibinski,Michael D Shields,Liam G Heaney,Peter V Coyle,Dara O'Donoghue

doi:10.1186/1743-422x-8-43

Rémi Villenave, Surendran Thavagnanam + Show 8 more

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https://doi.org/10.1186/1743-422x-8-43

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BackgroundHuman respiratory syncytial virus (RSV) causes severe respiratory disease in infants. Airway epithelial cells are the principle targets of RSV infection. However, the mechanisms by which it causes disease are poorly understood. Most RSV pathogenesis data are derived using laboratory-adapted prototypic strains. We hypothesized that such strains may be poorly representative of recent clinical isolates in terms of virus/host interactions in primary human bronchial epithelial cells (PBECs).MethodsTo address this hypothesis, we isolated three RSV strains from infants hospitalized with bronchiolitis and compared them with the prototypic RSV A2 in terms of cytopathology, virus growth kinetics and chemokine secretion in infected PBEC monolayers.ResultsRSV A2 rapidly obliterated the PBECs, whereas the clinical isolates caused much less cytopathology. Concomitantly, RSV A2 also grew faster and to higher titers in PBECs. Furthermore, dramatically increased secretion of IP-10 and RANTES was evident following A2 infection compared with the clinical isolates.ConclusionsThe prototypic RSV strain A2 is poorly representative of recent clinical isolates in terms of cytopathogenicity, viral growth kinetics and pro-inflammatory responses induced following infection of PBEC monolayers. Thus, the choice of RSV strain may have important implications for future RSV pathogenesis studies.

Highlights

Respiratory syncytial virus (RSV) infection is one of the leading causes of infant hospitalization
Substantial differences in primary human bronchial epithelial cells (PBECs) infectivity, virus growth kinetics and chemokine secretions, such as interferon-inducible protein 10 (IP-10/CXCL10), regulated upon activation, normal T cell expressed and secreted (RANTES/CCL5), interleukin 6 (IL-6) and IL-8 (CXCL8), were observed. These findings indicate that the use of respiratory syncytial virus (RSV) A2 in host-pathogen interaction studies might not be representative of recent RSV clinical isolates in terms of virus growth kinetics, cytopathic effects (CPE) and chemokine induction
Alignments of BT2a, BT3a and BT4a G protein sequences from amino acid 212 to the end of the sequence, along with representatives from each subgroup A and B genotypes, using Clustal 2.0 software determined that the clinical isolates belonged to genotypes GA5 (BT2a and BT4a) and GA2 (BT3a) (Figure 1)

Summary

Introduction

Respiratory syncytial virus (RSV) infection is one of the leading causes of infant hospitalization. RSV is increasingly recognized as a cause of severe illness in adults and especially the elderly [3]. The impact of RSV infections is probably underestimated, as early-life infections are associated with the development of recurrent wheeze (asthma) and allergy during childhood [4,5]. Human respiratory syncytial virus (RSV) causes severe respiratory disease in infants. Airway epithelial cells are the principle targets of RSV infection. Most RSV pathogenesis data are derived using laboratory-adapted prototypic strains. We hypothesized that such strains may be poorly representative of recent clinical isolates in terms of virus/host interactions in primary human bronchial epithelial cells (PBECs)

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