Huntingtin-interacting protein family members have a conserved pro-viral function from Caenorhabditis elegans to humans.
Huntingtin-interacting protein family members have a conserved pro-viral function from Caenorhabditis elegans to humans.
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亨廷顿蛋白相互作用蛋白家族成员具有从秀丽隐杆线虫到人类的保守的促病毒功能。
DOI：
10.1073/pnas.2006914117
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发表时间：
2020
影响因子：
11.1
通讯作者：
Wang,David
中科院分区：
文献类型：
--
作者：
Jiang,Hongbing;SandovalDelPrado,LuisEnrique;Leung,Christian;Wang,David
亨廷顿蛋白相互作用蛋白家族成员从酵母到人类在进化上都是保守的，它们被认为是网状蛋白介导的内吞作用的关键因素。在这里，我们鉴定了线虫线虫亨廷顿蛋白相互作用蛋白相关1(HIPR-1)是OSAY病毒感染OFC所必需的宿主因子。优雅女装。去除HIPR-1导致病毒RNA减少10,000多倍，这可以通过异位表达HIPR-1来挽救。从内源性转基因复制子系统复制的病毒RNA不受HIPR-1缺失的影响，这表明HIPR-1在复制前病毒生命周期的早期阶段发挥作用。HIPR-1突变体的异位表达表明，病毒感染既不需要分子筛轻链结合域，也不需要分子筛蛋白重链结合域，而肌醇磷脂结合域和F-肌动蛋白结合域是必需的。在人类细胞培养中，人类髋关节同源基因HIP1和HIP1R的缺失导致柯萨奇B3病毒的感染减少。最后，含有人HIP1 Anth(AP180 N-末端同源)结构域的嵌合HIPR-1的异位表达拯救了Orsay Inc.优雅，通过进化证明了它的功能的保守性。总的来说，这些发现进一步加深了我们对影响病毒感染的细胞因素的了解。优雅人和人类。
Huntingtin-interacting protein family members are evolutionarily conserved from yeast to humans, and they are known to be key factors in clathrin-mediated endocytosis. Here we identified theCaenorhabditis elegansprotein huntingtin-interacting protein-related 1 (HIPR-1) as a host factor essential for Orsay virus infection ofC. elegans. Ablation of HIPR-1 resulted in a greater than 10,000-fold reduction in viral RNA, which could be rescued by ectopic expression of HIPR-1. Viral RNA replication from an endogenous transgene replicon system was not affected by lack of HIPR-1, suggesting that HIPR-1 plays a role during an early, prereplication virus life-cycle stage. Ectopic expression of HIPR-1 mutants demonstrated that neither the clathrin light chain-binding domain nor the clathrin heavy chain-binding motif were needed for virus infection, whereas the inositol phospholipid-binding and F-actin–binding domains were essential. In human cell culture, deletion of the human HIP orthologs HIP1 and HIP1R led to decreased infection by Coxsackie B3 virus. Finally, ectopic expression of a chimeric HIPR-1 harboring the human HIP1 ANTH (AP180 N-terminal homology) domain rescued Orsay infection inC. elegans, demonstrating conservation of its function through evolution. Collectively, these findings further our knowledge of cellular factors impacting viral infection inC. elegansand humans.