Evolutionary conflicts between viruses and restriction factors shape immunity.
Evolutionary conflicts between viruses and restriction factors shape immunity.
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DOI：
10.1038/nri3295
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发表时间：
2012-10
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影响因子：
--
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中科院分区：
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限制因子是宿主表达的限制病毒复制的细胞内在基因。限制因子的特征在于其编码序列的快速进化（在病毒感染的正选择下）、其专门的抗病毒活性、其通常由干扰素诱导（尽管情况并非总是如此）以及在某些物种中中和其活性的病毒拮抗剂的存在。多种遗传机制使宿主能够跟上病毒适应的步伐，从而使病毒能够逃避限制因素。这些机制包括限制因子杂合性、限制因子基因的重复以及由于其对病毒适应性的影响而限制病毒进化。限制因素的进化使人们能够对古代病毒及其对人类祖先施加的选择压力做出推断。由于病毒比宿主进化得更快，现代脊椎动物的先天免疫系统通常针对过去的病毒感染进行了优化，而不一定针对现代世界当前的病毒威胁。宿主限制因子和病毒拮抗剂之间的进化“军备竞赛”留下了遗传“特征”，可以告诉我们很多关于过去和现在病毒感染的先天免疫反应的信息。宿主限制因子是有效的、广泛表达的细胞内病毒复制阻断剂，是针对病毒感染的先天免疫反应的重要组成部分。然而，病毒已经进化出对抗限制因素的机制。通过宿主生存和病毒复制的进化压力，进化的“军备竞赛”已经发展起来，推动了编码限制因子及其病毒拮抗剂的基因中有益突变的连续轮次选择。由于病毒的进化速度比宿主更快，因此现代脊椎动物的先天免疫系统在很大程度上经过优化以防御古老的病毒，而不是新的病毒威胁。因此，限制因素的进化史可能部分解释了为什么人类对现代世界中存在的病毒敏感或具有抵抗力。
Restriction factors are cell-intrinsic genes expressed by the host that limit virus replication. Restriction factors are characterized by the rapid evolution of their coding sequences (under positive selection from virus infection), by their dedicated antiviral activity, by their usual induction by interferons (although this is not always the case), and by the presence of viral antagonists that neutralize their activity in some species. Several genetic mechanisms allow the host to keep pace with virus adaptations that enable the virus to evade restriction factors. These mechanisms include restriction factor heterozygosity, the duplication of restriction factor genes, and the limitation of viral evolution as a result of its effects on viral fitness. The evolution of restriction factors allows one to make inferences about ancient viruses and the selection pressure that they exerted on human ancestors. Because viruses evolve faster than their hosts, the innate immune system of modern-day vertebrates is generally optimized for past virus infections and not necessarily for the current viral threats in the modern world. The evolutionary 'arms race' between host restriction factors and viral antagonists has left a genetic 'signature' that can tell us much about the innate immune response to past and present viral infections. Host restriction factors are potent, widely expressed intracellular blocks to viral replication that are an important component of the innate immune response to viral infection. However, viruses have evolved mechanisms that antagonize restriction factors. Through evolutionary pressure for both host survival and virus replication, an evolutionary 'arms race' has developed that drives continuous rounds of selection for beneficial mutations in the genes encoding restriction factors and their viral antagonists. Because viruses can evolve faster than their hosts, the innate immune system of modern-day vertebrates is for the most part optimized to defend against ancient viruses, rather than newer viral threats. Thus, the evolutionary history of restriction factors might, in part, explain why humans are susceptible or resistant to the viruses present in the modern world.
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DOI：
10.1073/pnas.0608289103
发表时间：
2006-11-07
影响因子：
11.1
作者：
Kamada, Kazuya;Igarashi, Tatsuhiko;Adachi, Akio
通讯作者：
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影响因子：
64.8
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影响因子：
6.7
作者：
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影响因子：
30.3
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Emerman M
影响因子：
56.9
作者：
Hatziioannou, Theodora;Princiotta, Michael;Bieniasz, Paul D.
通讯作者：
Bieniasz, Paul D.