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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Parvoviral virions deploy a capsid-tethered lipolytic enzyme to breach the endosomal membrane during cell entry.
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Parvoviral virions deploy a capsid-tethered lipolytic enzyme to breach the endosomal membrane during cell entry.

机译：细小病毒粒子在细胞进入过程中会部署衣壳连接的脂解酶，以破坏内体膜。

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摘要

Enveloped viruses deliver their virions into the host cell by fusion with the cellular plasma or endosomal membrane, thus creating topological continuity between the cytosol and the inside of the viral envelope. Nonenveloped viruses are, by their very nature, denied this strategy and must employ alternative methods to breach their host cell's delimiting membrane. We show here that the compact icosahedral parvoviral virion gains entry by deploying a lipolytic enzyme, phospholipase A(2) (PLA(2)), that is expressed at the N terminus of VP1, the minor coat protein. This region of VP1 is normally sequestered within the viral shell but is extruded during the entry process as a capsid-tethered domain. A single amino acid substitution in the active site of the VP1 PLA(2) inactivates enzymatic activity and abrogates infectivity. We have used transencapsidation of a vector expressing green fluorescent protein to show that infection by this PLA(2)-defective mutant can be complemented by coinfection with wild-typeor mutant full virions, provided they can express a functional PLA(2). Even though wild-type empty capsids contain an active form of the enzyme, it is not externalized under physiological conditions, and such capsids are not able to complement the PLA(2) mutant. Significantly, highly efficient rescue can be achieved by polyethyleneimine-induced endosome rupture or by coinfection with adenovirus as long as uptake of the two viruses is simultaneous and the adenovirus is capable of deploying pVI, a capsid protein with endosomolytic activity. Together, these results demonstrate a previously unrecognized enzymatic mechanism for nonenveloped virus penetration.
机译：包膜病毒通过与细胞质膜或内体膜融合而将其病毒粒子递送到宿主细胞中，从而在胞质溶胶和病毒包膜内部之间形成拓扑连续性。非包膜病毒本质上拒绝这种策略，必须采用其他方法破坏其宿主细胞的定界膜。我们在这里显示，紧凑的二十面体细小病毒颗粒通过部署脂解酶磷脂酶A（2）（PLA（2））（在次要外壳蛋白VP1的N末端表达）而获得进入。 VP1的此区域通常被隔离在病毒外壳内，但在进入过程中被作为衣壳连接域挤出。 VP1 PLA（2）的活性位点中的单个氨基酸取代可灭活酶活性并消除感染性。我们已经使用了表达绿色荧光蛋白的载体的转胶囊化，以显示该PLA（2）缺陷型突变体的感染可以与野生型或突变体完整病毒体共感染来补充，前提是它们可以表达功能性PLA（2）。即使野生型空衣壳包含酶的活性形式，它也不会在生理条件下外在化，并且这种衣壳不能补充PLA（2）突变体。重要的是，只要同时摄取两种病毒并且腺病毒能够部署具有内溶体活性的衣壳蛋白pVI，就可以通过聚乙烯亚胺诱导的内体破裂或腺病毒共感染来实现高效的抢救。总之，这些结果证明了对于非包膜病毒渗透的先前未被认识的酶促机制。

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