Induction of type I interferons and interferon-inducible Mx genes during respiratory syncytial virus infection and reinfection in cotton rats
Induction of type I interferons and interferon-inducible Mx genes during respiratory syncytial virus infection and reinfection in cotton rats
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DOI：
10.1099/vir.0.83294-0
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发表时间：
2008-01-01
影响因子：
3.8
通讯作者：
Blanco, Jorge C. G.
中科院分区：
文献类型：
--
作者：
Pletneva, Lioubov M.;Haller, Otto;Blanco, Jorge C. G.
呼吸道合胞病毒（RSV）是幼儿毛细支气管炎的主要原因。通常，RSV被认为是I型（α/β）干扰素（IFN）的不良诱导剂。体内感染期间活性I型IFN产生的测量是有要求的，因为产生了具有重叠活性的多种IFN亚型。相比之下，Mx基因的表达，这是严格调节I型IFN的表达，很容易确定。因此，本研究测量了Mx表达作为RSV感染期间棉鼠模型体内I型IFN活性的可靠替代标志物。结果表明，Mx基因的表达在感染动物的肺中以剂量和病毒株依赖性方式显著增强。Mx基因在肺中的表达被它们在鼻和脾中的诱导所抑制，尽管在脾中没有检测到同时的病毒基因表达。RSV免疫动物的再感染导致肺部病毒复制失败。因此，I型IFN和Mx基因表达在再感染动物中被触发，即使病毒不能从它们的肺中分离出来。此外，证明了对RSV的免疫力随时间减弱。病毒复制和Mx基因的表达变得更加突出，增加初次感染和再感染之间的间隔。这些结果突出了I型IFN在调节对RSV的免疫应答中的作用。
Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis in young children. In general, RSV is considered to be a poor inducer of type I (alpha/beta) interferons (IFNs). Measurement of active type I IFN production during infection in vivo is demanding, as multiple IFN subtypes with overlapping activities are produced. In contrast, Mx gene expression, which is tightly regulated by type I IFN expression, is easily determined. This study therefore measured Mx expression as a reliable surrogate marker of type I IFN activity during RSV infection in vivo in a cotton rat model. It was shown that expression of Mx genes was dramatically augmented in the lungs of infected animals in a dose- and virus strain-dependent manner. The expression of Mx genes in the lungs was paralleled by their induction in the nose and spleen, although in spleen no simultaneous virus gene expression was detected. Reinfection of RSV-immune animals leads to abortive virus replication in the lungs. Thus, type I IFN and Mx gene expression was triggered in reinfected animals, even though virus could not be isolated from their lungs. Furthermore, it was demonstrated that immunity to RSV wanes with time. Virus replication and Mx gene expression became more prominent with increasing intervals between primary infection and reinfection. These results highlight the role of type I IFN in modulation of the immune response to RSV.