Respiratory syncytial virus infects and abortively replicates in the lungs in spite of preexisting immunity
Respiratory syncytial virus infects and abortively replicates in the lungs in spite of preexisting immunity
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DOI：
10.1128/jvi.00102-07
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发表时间：
2007-09-01
影响因子：
5.4
通讯作者：
Blanco, Jorge C. G.
中科院分区：
文献类型：
--
作者：
Boukhvalova, Marina S.;Prince, Gregory A.;Blanco, Jorge C. G.
呼吸道合胞病毒（RSV）是幼儿毛细支气管炎和病毒性肺炎的主要原因，也是免疫功能低下个体和老年人的严重健康风险。对RSV的免疫力尚未完全了解。在这项工作中，我们建立了一种实时PCR监测RSV感染的方法，并应用该方法分析RSV在棉鼠模型中的体内复制，在幼稚动物和在动物提供免疫RSV先前RSV感染。我们发现，即使没有病毒可以从RSV攻击的免疫动物的肺中分离出来，RSV感染实际上发生了，并观察到病毒RNA转录物的积累。因此，这种类型的复制可以被称为“流产”，因为RSV能够进入免疫动物肺中的细胞，但后代病毒的产生受到损害。在未感染和再感染动物之间观察到RSV基因表达梯度的相似模式，表明病毒基因表达的mRNA梯度的偏斜（在其他病毒潜伏感染期间记录的机制）不太可能是再感染期间RSV复制失败的原因。我们发现，被动给予RSV抗体可预防通常伴随肺中病毒释放的生产性感染，但不能预防病毒的失败复制。据我们所知，这是RSV在体内复制失败的第一个证据。
Respiratory syncytial virus (RSV) is a major cause of bronchiolitis and viral pneumonia in young children and a serious health risk in immunocompromised individuals and the elderly. Immunity to RSV is not completely understood. In this work, we established a method for monitoring RSV infection by real-time PCR and applied this method for analysis of RSV replication in vivo in the cotton rat model in naive animals and in animals rendered immune to RSV by prior RSV infection. We found that even though no virus could be isolated from the lungs of RSV-challenged immune animals, RSV infection in fact took place and an accumulation of viral RNA transcripts was observed. This type of replication, therefore, can be termed "abortive," as RSV is capable of entering the cells in the lungs of immune animals, yet the production of progeny viruses is impaired. Similar patterns of RSV gene expression gradient were observed between naive and reinfected animals, indicating that the skewing of mRNA gradient of viral gene expression, a mechanism documented during latent infection by other viruses, is not likely to be responsible for abortive replication of RSV during reinfection. We found that passive administration of antibodies to RSV prevents productive infection normally accompanied by viral release in the lung, but it does not prevent abortive replication of the virus. To the best of our knowledge, this is the first evidence of abortive replication of RSV in vivo.