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病毒孔蛋白:发现、研究方法及宿主细胞膜通透性机制

Viroporins: discovery, methods of study, and mechanisms of host-membrane permeabilization.

作者信息

Alcaraz Antonio, Nieva José L

机构信息

Laboratory of Molecular Biophysics, Department of Physics, University Jaume I, Castellón, Spain.

Instituto Biofisika (CSIC-UPV/EHU), University of the Basque Country (UPV/EHU), Bilbao, Spain.

出版信息

Q Rev Biophys. 2025 Jan 14;58:e1. doi: 10.1017/S0033583524000192.

DOI:10.1017/S0033583524000192
PMID:39806799
Abstract

The 'Viroporin' family comprises a number of mostly small-sized, integral membrane proteins encoded by animal and plant viruses. Despite their sequence and structural diversity, viroporins share a common functional trend: their capacity to assemble transmembrane channels during the replication cycle of the virus. Their selectivity spectrum ranges from low-pH-activated, unidirectional proton transporters, to size-limited permeating pores allowing passive diffusion of metabolites. Through mechanisms not fully understood, expression of viroporins facilitates virion assembly/release from infected cells, and subverts the cell physiology, contributing to cytopathogenicity. Compounds that interact with viroporins and interfere with their membrane-permeabilizing activity , are known to inhibit virus production. Moreover, viroporin-defective viruses comprise a source of live attenuated vaccines that prevent infection by notorious human and livestock pathogens. This review dives into the origin and evolution of the viroporin concept, summarizes some of the methodologies used to characterize the structure-function relationships of these important virulence factors, and attempts to classify them on biophysical grounds attending to their mechanisms of ion/solute transport across membranes.

摘要

“病毒孔蛋白”家族由许多主要为小型的整合膜蛋白组成,这些蛋白由动植物病毒编码。尽管它们在序列和结构上存在多样性,但病毒孔蛋白具有一个共同的功能趋势:它们能够在病毒复制周期中组装跨膜通道。它们的选择性范围从低pH激活的单向质子转运体到允许代谢物被动扩散的大小受限的渗透孔。通过尚未完全了解的机制,病毒孔蛋白的表达促进病毒粒子从受感染细胞中组装/释放,并破坏细胞生理功能,导致细胞病变。已知与病毒孔蛋白相互作用并干扰其膜通透活性的化合物可抑制病毒产生。此外,缺乏病毒孔蛋白的病毒构成了减毒活疫苗的来源,可预防由臭名昭著的人类和家畜病原体引起的感染。本综述深入探讨了病毒孔蛋白概念的起源和演变,总结了一些用于表征这些重要毒力因子结构-功能关系的方法,并尝试根据它们跨膜离子/溶质转运机制在生物物理基础上对其进行分类。

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