Poxvirus-induced alteration of arachidonate metabolism.
Poxvirus-induced alteration of arachidonate metabolism.
复制标题
痘病毒诱导的花生四烯酸代谢改变。
DOI：
10.1073/pnas.90.5.2020
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发表时间：
1993
影响因子：
11.1
通讯作者：
R. Buller
中科院分区：
文献类型：
--
作者：
G. J. Palumbo;W. Glasgow;R. Buller
最近的证据表明，正痘病毒在体内和体外复制过程中对花生四烯酸代谢产物有一定的需求。我们的报告表明，一个病毒家族(痘病毒科)拥有多个基因，这些基因具有调节花生四烯酸代谢的功能。对感染牛痘病毒或牛痘病毒的BS-C-1细胞的分析发现，环氧合酶(特别是前列腺素E2和F2α)和脂氧合酶(特别是15-羟基二十碳四烯酸和12-羟基二十碳四烯酸)途径的花生四烯酸产物形成增加。相比之下，人类3型副流感或1型单纯疱疹病毒感染不会增加花生四烯酸代谢。结果与病毒早期基因产物直接介导或诱导宿主因子介导花生四烯酸代谢上调一致，尽管牛痘生长因子不起作用。此外，牛痘病毒38 kDa蛋白编码基因与抑制炎症反应有关，与抑制(14R，15S)-二羟基二十碳四烯酸的生物化学特征的产物的形成相关。我们认为，正痘病毒在感染过程中诱导花生四烯酸代谢上调，使感染细胞容易从环氧合酶和脂氧合酶途径产生炎症介质，因此，痘病毒至少有一个基因(38K)可以改变脂氧合酶-代谢物谱。
Recent evidence suggests that orthopoxviruses have an obligate requirement for arachidonic acid metabolites during replication in vivo and in vitro. Our report indicates that a virus family (Poxviridae) possesses multiple genes that function to regulate arachidonate metabolism. Analyses of BS-C-1 cells infected with cowpox virus or vaccinia virus detected enhanced arachidonate product formation from both the cyclooxygenase (specifically prostaglandins E2 and F2 alpha) and lipoxygenase (specifically 15-hydroxyeicosatetraenoic acid and 12-hydroxyeicosatetraenoic acid) pathways. In contrast, human parainfluenza type 3 or herpes simplex virus type 1 infections did not increase arachidonate metabolism. Results were consistent with a virus early-gene product either directly mediating or inducing a host factor that mediated the up-regulation of arachidonate metabolism, although vaccinia growth factor was not responsible. In addition, the cowpox virus 38-kDa protein-encoding gene, which is associated with inhibition of an inflammatory response, correlated with inhibition of formation of a product biochemically characteristic of (14R,15S)-dihydroxyeicosatetraenoic acid. We propose that orthopoxvirus-induced up-regulation of arachidonic acid metabolism during infection renders the infected cells susceptible to generation of inflammatory mediators from both the cyclooxygenase and the lipoxygenase pathways, and poxviruses, therefore, possess at least one gene (38K) that can alter the lipoxygenase-metabolite spectrum.