Elucidation of the roles of PTN and ISG15 in RSV cytopathogenesis: possible biomarkers of severe disease?. (360G-Wellcome-104516_Z_14_Z)

£212,118

Respiratory syncytial virus (RSV) is the commonest cause of severe lower respiratory tract infection in young infants, typically causing bronchiolitis and pneumonia. Prematurity is a risk factor for severe disease. How RSV causes human disease is poorly understood. Neonates, particularly preterms, are vulnerable to life-threatening infections and innate immune defences are critical. Innate immune responses are deficient in newborn infants relative to adults, with differential responses also evi dent between preterm versus term infants. RSV primarily targets airway epithelium and induces innate antiviral and pro-inflammatory chemokine responses. The host laboratory has developed a novel model of RSV infection based on well-differentiated primary paediatric nasal (WD-PNEC) epithelial cells that reproduces several hallmarks of severe disease. Using WD-PNECs derived from infants with histories of severe or mild RSV disease, microarray studies identified 2 genes that were differentially exp ressed between the cohorts, including ptn and isg15.The genes encode proteins with antiviral and/or anti-inflammatory properties. Preliminary data confirmed this differential expression and also suggest that these genes/proteins may be implicated in susceptibility to severe RSV infection.Therefore, this project will study the role of these genes/proteins in RSV cytopathogenesis, with particular emphasis on their expression kinetics, antiviral properties and the consequences of gene knockdown.

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Grant Details

Amount Awarded 212118
Applicant Surname Groves
Approval Committee Clinical Interview Committee
Award Date 2014-06-25T00:00:00+00:00
Financial Year 2013/14
Grant Programme: Title Research Training Fellowship
Internal ID 104516/Z/14/Z
Lead Applicant Dr Helen Groves
Partnership Value 212118
Planned Dates: End Date 2017-08-05T00:00:00+00:00
Planned Dates: Start Date 2014-08-06T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Northern Ireland
Sponsor(s) Prof Clifford Taggart