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Differential interferon gene expression in bronchiolitis caused by respiratory syncytial virus-A genotype ON1.
Medical Microbiology and Immunology ( IF 5.5 ) Pub Date : 2019-09-04 , DOI: 10.1007/s00430-019-00633-6
Alessandra Pierangeli 1 , Agnese Viscido 1 , Camilla Bitossi 1 , Federica Frasca 1 , Massimo Gentile 1 , Giuseppe Oliveto 1 , Antonella Frassanito 2 , Raffaella Nenna 2 , Fabio Midulla 2 , Carolina Scagnolari 1
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Bronchiolitis severity is determined by a complex interaction among viral replication and antiviral immunity. The current respiratory syncytial virus (RSV)-A, genotype ON1 demonstrated a high replicative capacity but seemed to be clinically less severe than the previously circulating RSV-A, NA1. To learn insights about ON1 innate immune response, we analyzed expression levels of type I/III interferon (IFN)-related genes in the respiratory mucosa of infants with RSV bronchiolitis. We enrolled RSV-positive bronchiolitis patients over 12 epidemic seasons at a university hospital in Rome. From nasopharyngeal washings’ cells (46 positive to NA1, 47 to ON1 and 28 to RSV-B, genotype BA), the mRNA copy number of the type III IFN receptor (IFNLR1 and IL10RB subunits), and of the type I/III IFN-stimulated genes, MxA and ISG56, was calculated using the threshold cycle relative quantification method with respect to an invariant gene. Expression levels of type III IFN receptor subunits genes positively correlated to each other and did not differ in infants infected with different RSV genotypes. The ISGs levels also positively correlated between them but differed among groups. MxA levels were significantly higher in NA1-infected infants than in those with ON1 and BA; ISG56 expression was slightly higher in NA1 than in the other strains. Interestingly, a moderate negative correlation existed between viral load and both ISGs values in ON1-infected infants only. The reduced ISG levels elicited during infections with ON1 (and BA) may cause a weaker control of RSV replication and/or an inadequate host immune response which may impact the risk of respiratory sequelae.

中文翻译:

呼吸道合胞病毒A基因型ON1引起的细支气管炎中干扰素基因的差异表达。

细支气管炎的严重程度取决于病毒复制和抗病毒免疫之间的复杂相互作用。当前的呼吸道合胞病毒(RSV)-A基因型ON1具有高复制能力,但在临床上似乎不如以前流行的RSV-A NA1严重。为了了解ON1先天性免疫应答的见解,我们分析了RSV毛细支气管炎婴儿呼吸道粘膜中I / III型干扰素(IFN)相关基因的表达水平。我们在罗马的一家大学医院中将12个流行季节中的RSV阳性细支气管炎患者纳入研究。从鼻咽冲洗液的细胞(NA1阳性46,ON1阳性47,RSV-B阳性,BA基因型28),III型IFN受体(IFNLR1和IL10RB亚基)和I / III IFN型的mRNA拷贝数受刺激的基因MxA和ISG56,对于不变基因,使用阈值循环相对定量方法计算出Δβ。III型IFN受体亚基基因的表达水平彼此正相关,在感染了不同RSV基因型的婴儿中没有差异。ISGs水平之间也呈正相关,但各组之间不同。NA1感染婴儿的MxA水平显着高于ON1和BA婴儿。在NA1中,ISG56表达略高于其他菌株。有趣的是,仅在ON1感染的婴儿中,病毒载量和两个ISG值之间存在中等程度的负相关。在感染ON1(和BA)的过程中引起的ISG水平降低可能会导致RSV复制控制较弱和/或宿主免疫反应不足,从而影响呼吸后遗症的风险。
更新日期:2019-09-04
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