Department of Pediatrics, Akershus University Hospital, Lørenskog, Norway.
BMC Infect Dis. 2011 Mar 8;11:59. doi: 10.1186/1471-2334-11-59.
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 Dicer. In order to further investigate whether reduced Dicer expression can predispose newborns to RSV disease, we have analyzed the gene expression of Dicer in the cord blood of 37 infants with confirmed RSV 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.
呼吸道合胞病毒(RSV)是发达国家小儿住院的重要病因之一。核糖核酸酶 Dicer 通过 RNA 干扰是基因表达和细胞功能的重要调节因子,也可能具有抗病毒功能。对 5 例 RSV 病患儿脐带血的微阵列分析显示 Dicer 下调。为了进一步研究 Dicer 表达减少是否会使新生儿易患 RSV 病,我们分析了 37 例确诊 RSV 病新生儿脐带血中 Dicer 的基因表达。
收集了 2108 名新生儿的脐带血。51 例 RSV 鼻咽抽吸物阳性<1 岁,根据疾病严重程度分组。37 例有足够的高质量脐带血 RNA。采用 TaqMan 低密度阵列对脐带血进行 qPCR 分析,评估 Dicer 基因表达,并与未发生 RSV 病的对照婴儿进行 Mann-Whitney 检验比较。
严重疾病组 Dicer 显著下调:相对数量 0.69(95%CI:0.56-0.87),p=0.002。轻症疾病组无明显下调。
我们在 RSV 暴露前就发现重症 RSV 病婴儿脐带血中 Dicer 表达减少。我们推测,这可能通过白细胞基因调控的破坏或直接抗病毒 RNA 干扰机制使 RSV 病易感性增加。