Comparative analysis of innate immune responses following infection of newborn calves with bovine rotavirus and bovine coronavirus
Comparative analysis of innate immune responses following infection of newborn calves with bovine rotavirus and bovine coronavirus
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DOI：
10.1099/vir.0.82861-0
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发表时间：
2007-10-01
影响因子：
3.8
通讯作者：
Griebel, Philip
中科院分区：
文献类型：
--
作者：
Aich, Palok;Wilson, Heather L.;Griebel, Philip
牛轮状病毒(BRV)和牛冠状病毒(BCV)是引起新生犊牛腹泻和死亡的重要原因，虽然这两种病毒属于不同的病毒类别，但它们都感染肠道上皮细胞，并引起相似的临床症状。轮状病毒通常会引起急性感染，但冠状病毒感染可以持续并在成人中反复发生。病毒结构和临床结果的差异促使我们假设轮状病毒和冠状病毒感染后的先天性粘膜免疫反应将明显不同。为了解决这一假设，研究人员分析了BRV和BCV感染后1天大的剥夺初乳的小牛经手术准备的肠环中的基因表达。用牛cDNA微阵列分析感染后18h的基因表达谱；大多数差异表达的显著基因与细胞周期和先天免疫反应有关。通过实时定量聚合酶链式反应(qRT-PCR)对其中的一组基因进行验证。通过qRT-PCR进一步分析与干扰素(IFN)、细胞因子和Toll样受体相关的基因的表达。在BRV感染的宿主组织中，TLR3、IL-6和P65有较强的激活，而在BCV感染的组织中则没有。这两种病毒也下调了干扰素和促炎细胞因子相关的途径。体外研究证实，干扰素可抑制病毒复制。所有这些结果表明，要么在感染后18h观察到宿主反应的非常早期的事件，要么两种病毒都有独特的有效策略来逃避宿主免疫反应。
Bovine rotavirus (BRV) and bovine coronavirus (BCV) are important causes of diarrhoea and death in newborn calves, Although these viruses belong to distinct viral classes, they both infect intestinal epithelial cells and induce similar clinical symptoms. Rotavirus usually causes an acute infection, but coronavirus infection can persist and reoccur in adults. Differences in viral structure and clinical outcome prompted us to postulate that innate mucosal immune responses would be markedly different following rotavirus and coronavirus infections. To address this hypothesis, gene expression following BRV and BCV infection was analysed in surgically prepared intestinal loops from 1 -day-old colostrum-deprived calves. Gene expression was profiled at 18 h post-infection using bovine cDNA microarrays; the majority of differentially expressed significant genes were associated with the cell cycle and innate immune responses. A select group of these genes was validated by quantitative real-time PCR (qRT-PCR). The expression of genes associated with interferons (IFNs), cytokines and Toll-like receptors, which were not present on the microarray, was analysed further by qRT-PCR. Strong activation of TLR3, IL-6 and p65 was observed in BRV-infected host tissues, but not in tissues infected with BCV. Both viruses also downregulated IFN- and pro-inflammatory cytokine-associated pathways. In vitro studies confirmed that IFN inhibited viral replication. All of these results together suggested either that very early events of host responses at 18 h post-infection were being observed, or that both viruses have unique effective strategies to evade host immune responses.