Host transcription profiles upon primary respiratory syncytial virus infection
Host transcription profiles upon primary respiratory syncytial virus infection
复制标题
DOI：
10.1128/jvi.02220-06
复制
发表时间：
2007-06-01
影响因子：
5.4
通讯作者：
Hoebee, Barbara
中科院分区：
文献类型：
--
作者：
Janssen, Riny;Pennings, Jeroen;Hoebee, Barbara
呼吸道合胞病毒（RSV）是儿童严重下呼吸道感染的常见原因。重度RSV疾病与对RSV的不适当免疫应答相关，导致受宿主遗传因素影响的肺病理学增强。为了深入了解RSV感染的发病机制和免疫应答的早期途径，我们确定了小鼠感染后第1天和第3天肺和淋巴结的转录谱。原发性RSV感染导致快速但短暂的先天性促炎反应，如诱导大量I型干扰素调节基因和趋化因子基因、参与炎症的基因和参与抗原加工的基因所示。有趣的是，这种反应在感染后第1天比第3天强得多，表明肺中的强转录反应先于病毒复制的高峰。令人惊讶的是，下调基因的集合很小，并且这些基因中没有一个显示出强烈的下调。肺引流淋巴结中的反应远不如肺反应显著，提示NK细胞活化。我们的数据表明，在病毒复制高峰和炎症细胞流入之前的时间点，在转录水平上测量的局部肺反应已经减弱。RSV感染后不久诱导的过程和途径现在可以用于选择候选基因，用于严重RSV感染儿童的人类遗传学研究。
Respiratory syncytial virus (RSV) is a common cause of severe lower respiratory tract infection in children. Severe RSV disease is related to an inappropriate immune response to RSV resulting in enhanced lung pathology which is influenced by host genetic factors. To gain insight into the early pathways of the pathogenesis of and immune response to RSV infection, we determined the transcription profiles of lungs and lymph nodes on days 1 and 3 after infection of mice. Primary RSV infection resulted in a rapid but transient innate, proinflammatory response, as exemplified by the induction of a large number of type I interferon-regulated genes and chemokine genes, genes involved in inflammation, and genes involved in antigen processing. Interestingly, this response is much stronger on day 1 than on day 3 after infection, indicating that the strong transcriptional response in the lung precedes the peak of viral replication. Surprisingly, the set of downregulated genes was small and none of these genes displayed strong down-regulation. Responses in the lung-draining lymph nodes were much less prominent than lung responses and are suggestive of NK cell activation. Our data indicate that at time points prior to the peak of viral replication and influx of inflammatory cells, the local lung response, measured at the transcriptional level, has already dampened down. The processes and pathways induced shortly after RSV infection can now be used for the selection of candidate genes for human genetic studies of children with severe RSV infection.