Induction of apoptosis limits cytomegalovirus cross-species infection
Induction of apoptosis limits cytomegalovirus cross-species infection
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DOI：
10.1038/sj.emboj.7601133
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发表时间：
2006-06-07
期刊：
影响因子：
11.4
通讯作者：
Brune, Wolfram
中科院分区：
文献类型：
--
作者：
Jurak, Igor;Brune, Wolfram
跨物种感染是大多数新出现和重新出现的病毒性疾病的原因。然而，人们对限制病毒在特定宿主物种中的机制知之甚少，以及病毒跨越物种屏障并在不同宿主中复制所需的因素。巨细胞病毒（CMV）是高度物种特异性的β-疱疹病毒的代表。它们只在自己的细胞或密切相关的物种中复制。在这项研究中，巨细胞病毒种属特异性的分子机制进行了研究。我们发现，感染人类细胞与鼠巨细胞病毒（MCMV）触发的内在凋亡途径，涉及半胱天冬酶-9激活。如果细胞凋亡被Bcl-2或功能类似的蛋白质阻断，MCMV可以打破物种屏障并在人类细胞中复制。编码线粒体凋亡抑制剂的人巨细胞病毒的单个基因足以允许MCMV在人细胞中复制。此外，相同的原理促进大鼠巨细胞病毒在人类细胞中的复制。因此，诱导细胞凋亡作为一种先天性免疫防御，以抑制啮齿动物CMV的跨种感染。
Cross-species infections are responsible for the majority of emerging and re-emerging viral diseases. However, little is known about the mechanisms that restrict viruses to a certain host species, and the factors viruses need to cross the species barrier and replicate in a different host. Cytomegaloviruses ( CMVs) are representatives of the beta-herpesviruses that are highly species specific. They replicate only in cells of their own or a closely related species. In this study, the molecular mechanism underlying the cytomegalovirus species specificity was investigated. We show that infection of human cells with the murine cytomegalovirus ( MCMV) triggers the intrinsic apoptosis pathway involving caspase-9 activation. MCMV can break the species barrier and replicate in human cells if apoptosis is blocked by Bcl-2 or a functionally analogous protein. A single gene of the human cytomegalovirus encoding a mitochondrial inhibitor of apoptosis is sufficient to allow MCMV replication in human cells. Moreover, the same principle facilitates replication of the rat cytomegalovirus in human cells. Thus, induction of apoptosis serves as an innate immune defense to inhibit cross-pecies infections of rodent CMVs.