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

<p>Abstract</p> <p>Background</p> <p>Respiratory syncytial virus (RSV) is one of the most important causes of pediatric hospital admissions in the developed world. The ribonuclease Dicer is an important regulator of gene expression and cellular function via RNA interference, and may also have anti-viral functions. A previous microarray analysis of the cord blood of 5 patients with RSV disease suggested downregulation of <it>Dicer</it>. In order to further investigate whether reduced <it>Dicer </it>expression can predispose newborns to RSV disease, we have analyzed the gene expression of <it>Dicer </it>in the cord blood of 37 infants with confirmed RSV disease.</p> <p>Methods</p> <p>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. <it>Dicer </it>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.</p> <p>Results</p> <p>There was significant downregulation of <it>Dicer </it>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.</p> <p>Conclusions</p> <p>We demonstrate reduced <it>Dicer </it>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.</p

Acute bronchiolitis in infancy as risk factor for wheezing and reduced pulmonary function by seven years in Akershus County, Norway

BACKGROUND: Acute viral bronchiolitis is one of the most common causes of hospitalisation during infancy in our region with respiratory syncytial virus (RSV) historically being the major causative agent. Many infants with early-life RSV bronchiolitis have sustained bronchial hyperreactivity for many years after hospitalisation and the reasons for this are probably multifactorial. The principal aim of the present study was to investigate if children hospitalised for any acute viral bronchiolitis during infancy in our region, and not only those due to RSV, had more episodes of subsequent wheezing up to age seven years and reduced lung function at that age compared to children not hospitalised for acute bronchiolitis during infancy. A secondary aim was to compare the hospitalised infants with proven RSV bronchiolitis (RS+) to the hospitalised infants with non-RSV bronchiolitis (RS-) according to the same endpoints. METHODS: 57 infants hospitalised at least once with acute viral bronchiolitis during two consecutive winter seasons in 1993–1994 were examined at age seven years. An age-matched control group of 64 children, who had not been hospitalised for acute viral bronchiolitis during infancy, were recruited from a local primary school. Epidemiological and clinical data were collected retrospectively from hospital discharge records and through structured clinical interviews and physical examinations at the follow-up visit. RESULTS: The children hospitalised for bronchiolitis during infancy had decreased lung function, more often wheezing episodes, current medication and follow-up for asthma at age seven years than did the age matched controls. They also had lower average birth weight and more often first order family members with asthma. We did not find significant differences between the RSV+ and RSV- groups. CONCLUSION: Children hospitalised for early-life bronchiolitis are susceptible to recurrent wheezing and reduced pulmonary function by seven years compared to age-matched children not hospitalised for early-life bronchiolitis. We propose that prolonged bronchial hyperreactivity could follow early-life RSV negative as well as RSV positive bronchiolitis

Nasal mucosal microRNA expression in children with respiratory syncytial virus infection

Background Respiratory syncytial virus (RSV) infection is a common cause of pediatric hospitalization. microRNA, key regulators of the immune system, have not previously been investigated in respiratory specimens during viral infection. We investigated microRNA expression in the nasal mucosa of 42 RSV-positive infants, also comparing microRNA expression between disease severity subgroups. Methods Nasal mucosa cytology specimens were collected from RSV-positive infants and healthy controls. 32 microRNA were selected by microarray for qPCR verification in 19 control, 16 mild, 7 moderate and 19 severe disease samples. Results Compared to healthy controls, RSV-positive infants downregulated miR-34b, miR-34c, miR-125b, miR-29c, mir125a, miR-429 and miR-27b and upregulated miR-155, miR-31, miR-203a, miR-16 and let-7d. On disease subgroups analysis, miR-125a and miR-429 were downregulated in mild disease (p = 0.03 and 0.02, respectively), but not in severe disease (p = 0.3 and 0.3). Conclusion microRNA expression in nasal epithelium cytology brushings of RSV-positive infants shows a distinct profile of immune-associated miRNA. miR-125a has important functions within NF-κB signaling and macrophage function. The lack of downregulation of miR-125a and miR-429 in severe disease may help explain differences in disease manifestations on infection with RSV