Crimean-Congo hemorrhagic fever virus delays activation of the innate immune response
Crimean-Congo hemorrhagic fever virus delays activation of the innate immune response
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DOI：
10.1002/jmv.21222
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发表时间：
2008-08-01
影响因子：
12.7
通讯作者：
Mirazimi, Ali
中科院分区：
文献类型：
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作者：
Andersson, Ida;Karlberg, Helen;Mirazimi, Ali
作为抵抗病毒感染的第一道防线，哺乳动物细胞引发先天免疫应答，其特征在于I型干扰素的分泌和干扰素刺激基因的上调。许多病毒下调先天免疫应答以增强其毒力。克里米亚-刚果出血热病毒（CCHFV）是布尼亚病毒科的一种内罗病毒属病毒，是人类严重出血热的病原体，死亡率高。关于针对CCHFV的先天免疫应答的知识是最有限的。有趣的是，在这项研究中，它表明，复制CCHFV延迟基本上IFN的反应，可能是通过干扰IRF-3的激活途径。此外，它表明，CCHFV复制几乎是不敏感的后续治疗干扰素-α。一旦病毒复制，病毒复制或多或少对干扰素诱导的抗病毒作用不敏感。通过使用干扰素生物测定，显示感染的细胞在感染后相对较晚分泌干扰素，即感染后48小时。总之，结果表明存在由CCHFV编码的毒力因子，其延迟宿主防御以允许病毒在宿主中快速传播。
As a first line of defence against virus infection, mammalian cells elicit an innate immune response, characterized by secretion of type I interferons and the up-regulation of interferon stimulated genes. Many viruses down-regulate the innate immune responses in order to enhance their virulence. Crimean-Congo hemorrhagic fever virus (CCHFV), a Nairovirus of the family Bunyaviridae is the causative agent of severe hemorrhagic fever in humans with high mortality. Knowledge regarding the innate immune response against CCHFV is most limited. Interestingly, in this study it is shown that replicating CCHFV delays substantially the IFN response, possibly by interfering with the activation pathway of IRF-3. In addition, it is demonstrated that CCHFV replication is almost insensitive to subsequent treatment with interferon-alpha. Once the virus is replicating, virus replication is more or less insensitive to the antiviral effects induced by the interferon. By using an interferon bioassay, it is shown that infected cells secrete interferon relatively late after infection, that is, 48 hr post-infection. In summary, the results suggest the presence of a virulence factor encoded by CCHFV that delays the host defence in order to allow rapid viral spread in the host.