The function and evolution of the restriction factor Viperin in primates was not driven by lentiviruses.
The function and evolution of the restriction factor Viperin in primates was not driven by lentiviruses.
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DOI：
10.1186/1742-4690-9-55
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发表时间：
2012-06-26
期刊：
影响因子：
3.3
通讯作者：
Emerman M
中科院分区：
文献类型：
--
作者：
Lim ES;Wu LI;Malik HS;Emerman M
维珀林（Viperin），也称为RSAD2，是一种干扰素诱导性蛋白质，它能有效抑制多种不同的病毒，如流感病毒、丙型肝炎病毒、人巨细胞病毒和西尼罗河病毒。据认为，维珀林通过改变细胞内的脂质环境来影响病毒出芽。由于HIV - 1和其他逆转录病毒依赖宿主细胞的脂质区域进行出芽和感染，我们研究了维珀林是否也能抑制人类免疫缺陷病毒和其他逆转录病毒的可能性。
像其他具有广泛抗病毒范围的宿主限制因子一样，我们发现维珀林在灵长类动物中也一直在正选择作用下进化。正选择的模式表明维珀林在灵长类动物进化过程中逃避了多种病毒拮抗剂。此外，我们发现维珀林在HIV主要靶细胞中是由干扰素诱导产生的。我们表明，维珀林的外源表达在病毒从细胞释放阶段抑制了HIV - 1的LAI毒株。然而，维珀林的抑制作用具有高度的毒株特异性，并不影响大多数HIV - 1毒株或其他所测试的逆转录病毒。而且，在淋巴细胞系中敲低内源性维珀林并没有显著影响HIV - 1的传播感染。
尽管在灵长类动物进化过程中正选择作用于维珀林，但我们的研究结果表明，维珀林不是针对HIV - 1和其他逆转录病毒的主要限制因子。因此，其他病毒谱系可能是灵长类动物中维珀林正选择进化特征的原因。
Viperin, also known as RSAD2, is an interferon-inducible protein that potently restricts a broad range of different viruses such as influenza, hepatitis C virus, human cytomegalovirus and West Nile virus. Viperin is thought to affect virus budding by modification of the lipid environment within the cell. Since HIV-1 and other retroviruses depend on lipid domains of the host cell for budding and infectivity, we investigated the possibility that Viperin also restricts human immunodeficiency virus and other retroviruses. Like other host restriction factors that have a broad antiviral range, we find that viperin has also been evolving under positive selection in primates. The pattern of positive selection is indicative of Viperin's escape from multiple viral antagonists over the course of primate evolution. Furthermore, we find that Viperin is interferon-induced in HIV primary target cells. We show that exogenous expression of Viperin restricts the LAI strain of HIV-1 at the stage of virus release from the cell. Nonetheless, the effect of Viperin restriction is highly strain-specific and does not affect most HIV-1 strains or other retroviruses tested. Moreover, knockdown of endogenous Viperin in a lymphocytic cell line did not significantly affect the spreading infection of HIV-1. Despite positive selection having acted on Viperin throughout primate evolution, our findings indicate that Viperin is not a major restriction factor against HIV-1 and other retroviruses. Therefore, other viral lineages are likely responsible for the evolutionary signatures of positive selection in viperin among primates.
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影响因子：
15.9
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