RTP4 Is a Potent IFN-Inducible Anti-flavivirus Effector Engaged in a Host-Virus Arms Race in Bats and Other Mammals.
RTP4 Is a Potent IFN-Inducible Anti-flavivirus Effector Engaged in a Host-Virus Arms Race in Bats and Other Mammals.
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DOI：
10.1016/j.chom.2020.09.014
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发表时间：
2020-11-11
影响因子：
30.3
通讯作者：
Schoggins JW
中科院分区：
文献类型：
--
作者：
Boys IN;Xu E;Mar KB;De La Cruz-Rivera PC;Eitson JL;Moon B;Schoggins JW
在哺乳动物中，蝙蝠尤其富含人畜共患病毒，包括黄病毒。某些蝙蝠物种可以有效但无症状地感染病毒，而这些病毒会在其他物种中引起明显的疾病。然而，相对于其他哺乳动物，人们对蝙蝠的抗病毒效应子库知之甚少。在此，我们报告黑飞狐受体转运蛋白 4 (RTP4) 作为黄病毒科人类病原体（包括寨卡病毒、西尼罗河病毒和丙型肝炎病毒）的有效 IFN 诱导抑制剂。从机制上讲，RTP4 与黄病毒复制酶结合，结合病毒 RNA，并抑制病毒基因组扩增。比较方法表明，RTP4 正在经历正选择，黄病毒可以突变以逃避 RTP4 施加的限制，并且不同的哺乳动物 RTP4 直向同源物表现出针对不同黄病毒科成员的惊人特异性模式。我们的研究结果揭示了一种抗病毒机制，该机制可能适应了哺乳动物一亿多年的进化，以适应独特的宿主病毒遗传冲突。病毒与其宿主之间的冲突推动了抗病毒限制因素的进化。男孩等人。揭示了哺乳动物 RTP4 作为一种抗病毒效应子，它以物种特异性的方式抑制不同黄病毒的复制，从而凸显了跨越 1 亿年哺乳动物进化过程中未受重视的宿主-病原体分子军备竞赛。
Among mammals, bats are particularly rich in zoonotic viruses, including flaviviruses. Certain bat species can be productively yet asymptomatically infected with viruses that cause overt disease in other species. However, little is known about the antiviral effector repertoire in bats relative to other mammals. Here we report the black flying fox Receptor Transporter Protein 4 (RTP4) as a potent IFN-inducible inhibitor of human pathogens in the Flaviviridae family, including Zika, West Nile, and hepatitis C viruses. Mechanistically, RTP4 associates with the flavivirus replicase, binds viral RNA, and suppresses viral genome amplification. Comparative approaches revealed that RTP4 is undergoing positive selection, that a flavivirus can mutate to escape RTP4-imposed restriction, and that diverse mammalian RTP4 orthologs exhibit striking patterns of specificity against distinct Flaviviridae members. Our findings reveal an antiviral mechanism that has likely adapted over 100 million years of mammalian evolution to accommodate unique host-virus genetic conflicts. Conflicts between viruses and their hosts drive the evolution of antiviral restriction factors. Boys et al. unveil mammalian RTP4 as an antiviral effector that suppresses the replication of distinct flaviviruses in a species-specific manner, thus highlighting an unappreciated host-pathogen molecular arms race spanning 100 million years of mammalian evolution.
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影响因子：
3.7
作者：
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10.1073/pnas.0804106105
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