Pletneva Lioubov M, Haller Otto, Porter David D, Prince Gregory A, Blanco Jorge C G
Virion Systems Inc., 9610 Medical Center Drive, Suite 100, Rockville, MD 20850, USA.
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79008 Freiburg, Germany.
J Gen Virol. 2008 Jan;89(Pt 1):261-270. doi: 10.1099/vir.0.83294-0.
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.
呼吸道合胞病毒（RSV）是幼儿细支气管炎的主要病因。一般来说，RSV被认为是I型（α/β）干扰素（IFN）的较弱诱导剂。由于感染期间会产生多种具有重叠活性的IFN亚型，因此在体内感染过程中测量活性I型IFN的产生具有一定难度。相比之下，受I型IFN表达严格调控的Mx基因表达则易于测定。因此，本研究在棉鼠模型中测量了Mx表达，作为RSV体内感染期间I型IFN活性的可靠替代标志物。结果表明，Mx基因的表达在受感染动物的肺中以剂量和病毒株依赖的方式显著增加。Mx基因在肺中的表达与其在鼻和脾中的诱导情况相似，尽管在脾中未检测到同时存在的病毒基因表达。RSV免疫动物的再次感染导致肺中病毒复制失败。因此，即使在再次感染的动物肺中无法分离出病毒，I型IFN和Mx基因表达仍被触发。此外还证明，对RSV的免疫力会随时间减弱。随着初次感染和再次感染之间间隔时间的增加，病毒复制和Mx基因表达变得更加显著。这些结果突出了I型IFN在调节对RSV免疫反应中的作用。
