Rhinovirus infects primary human airway fibroblasts and induces a neutrophil chemokine and a permeability factor

Autor: Dinesha de Silva, Philip G. Bardin, Nicholas Freezer, Hayat Dagher, John W Wilson, Reena Ghildyal, Xun Li, Howard Donninger
Rok vydání: 2005
Předmět:
Zdroj: Journal of Medical Virology. 75:608-615
ISSN: 1096-9071
0146-6615
DOI: 10.1002/jmv.20315
Popis: The events linking rhinovirus (RV) infection to airway symptoms are poorly understood. The virus initially infects airway epithelium followed by a vigorous inflammatory response that may entail spread of RV from epithelium to other cells in the airway wall. However, RV has fastidious growth characteristics and to date reproductive infection of primary cells other than human airway epithelium has not been confirmed. Airway fibroblasts are adjacent to and in contact with epithelial cells, play a key role in innate immune responses, and may participate in the evolution of inflammation. To investigate fibroblast actions, we first determined whether RV could infect and replicate in primary culture human lung fibroblasts. RV serotype 16 (RV16) was used to infect fibroblasts grown from lung tissue, and virus infection with replication was demonstrated by a combination of techniques. RT-PCR was used to show an increase in RV transcription; confocal microscopy demonstrated colocalization of the replicative form of RV genome (double-stranded RNA) and RV16 proteins; infectious virus was also recovered from the culture supernatant of infected fibroblasts. Functional consequences of RV infection were next examined. RV infection of fibroblasts was followed by an increase in epithelial neutrophil-activating peptide-78 (ENA-78) mRNA and protein. The permeability factor vascular endothelial growth factor (VEGF) was also induced over a similar time course. These data suggest that interactions between RV and human fibroblasts are feasible, may coordinate neutrophil chemoattraction with enhanced vascular permeability and that fibroblasts may contribute to inflammatory responses following RV infections.
Databáze: OpenAIRE
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