Reduced Dicer expression in the cord blood of infants admitted with severe respiratory syncytial virus disease

The cord blood of 2108 newborns was collected. 51 had a positive nasopharyngeal aspirate for RSV <1 year, and were grouped according to disease severity. 37 had sufficient cord blood RNA of good quality. Dicer gene expression was assessed by qPCR analysis of cord blood using a TaqMan low-density array and compared to control infants who did not present with RSV disease using the Mann-Whitney test.There was significant downregulation of Dicer in the severe disease group: relative quantity 0.69 (95% CI: 0.56 - 0.87), p = 0.002. There was no significant downregulation in the mild disease group.We demonstrate reduced Dicer expression in the cord blood of infants with severe RSV disease, prior to RSV exposure. We theorize that this may predispose to RSV disease by disruption of leukocyte gene regulation or direct anti-viral RNA interference mechanisms.Bronchiolitis and other lower respiratory tract diseases are amongst the most common causes of pediatric admissions [1,2]. In epidemiological studies the most important pathogen causing bronchiolitis has consistently been respiratory syncytial virus (RSV) [1,3-7]. The yearly epidemics of RSV lead to a significant increase in admissions to pediatric wards across the globe during the winter and spring months. Infantile RSV bronchiolitis is associated with later development of asthma in childhood [8], and is therefore a major cause of ongoing disease burden to patients and significant health costs to society [5].69% of US children are infected with RSV in the first year of life, and almost all by the age of two years [6]. The majority are asymptomatic or have only mild symptoms. International studies estimate the annual incidence of RSV bronchiolitis requiring hospital admission to 22 - 31/1000 amongst infants < 1 year [2,6,9,10].Why so few children exposed to RSV should develop symptoms requiring hospital admission is yet to be adequately explained, although research has provided important clues in the last 10 years. Some gen