A mechanism for the inhibition of fever by a virus
A mechanism for the inhibition of fever by a virus
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DOI：
10.1073/pnas.93.20.11029
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发表时间：
1996-10-01
影响因子：
11.1
通讯作者：
Smith, GL
中科院分区：
文献类型：
--
作者：
Alcami, A;Smith, GL
痘病毒编码的蛋白质可阻断细胞因子的活性，对这种致病因子的研究不仅有助于我们了解病毒的致病机制，而且有助于了解细胞因子的生理作用。发热是对感染的一种非特异性反应，有助于宿主防御。几种细胞因子注射到动物体内会引起体温升高，但在自然发生的发热中，很难证明任何细胞因子都有关键作用。我们描述了第一个病毒抑制发热及其分子机制的例子，包括天花疫苗在内的几种痘苗病毒株表达可溶性白介素1受体。它能结合IL-1β，但不能结合IL-1α。这些病毒防止感染的小鼠的发热反应，而自然或通过基因工程缺乏受体的菌株会引起发热，修复天花疫苗哥本哈根中存在缺陷的IL-1β抑制剂，哥本哈根是一种比广泛使用的疫苗菌株Wyeth和Lister更强的病毒，可以抑制发烧和减轻疾病，而疫苗诱导的发热可以用IL-1β的抗体抑制。这些发现提供了强有力的证据，表明IL-1β而不是其他细胞因子是痘病毒感染的主要内源性热原。
Poxviruses encode proteins that block the activity of cytokines, Here we show that the study of such virulence factors can contribute to our understanding of not only virus pathogenesis but also the physiological role of cytokines, Fever is a nonspecific response to infection that contributes to host defense, Several cytokines induce an elevation of body temperature when injected into animals, but in naturally occurring fever it has been difficult to show that any cytokine has a critical role, We describe the first example of the suppression of fever by a virus and the molecular mechanism leading to it, Several vaccinia virus strains including smallpox vaccines express soluble interleukin 1 (IL-1) receptors, which bind IL-1 beta but not IL-1 alpha. These viruses prevent the febrile response in infected mice, whereas strains that naturally or through genetic engineering lack the receptor induce fever, Repair of the defective IL-1 beta inhibitor in the smallpox vaccine Copenhagen, a more virulent virus than the widely used vaccine strains Wyeth and Lister, suppresses fever and attenuates the disease, The vaccinia-induced fever was inhibited with antibodies to IL-1 beta. These findings provide strong evidence that IL-1 beta, and not other cytokines, is the major endogenous pyrogen in a poxvirus infection.