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利用基于细菌的生物测定从致病性病毒中筛选潜在的病毒孔道蛋白候选物

Potential Viroporin Candidates From Pathogenic Viruses Using Bacteria-Based Bioassays.

机构信息

Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus Givat-Ram, Jerusalem 91904, Israel.

出版信息

Viruses. 2019 Jul 9;11(7):632. doi: 10.3390/v11070632.

Abstract

Viroporins are a family of small hydrophobic proteins found in many enveloped viruses that are capable of ion transport. Building upon the ability to inhibit influenza by blocking its archetypical M2 H channel, as a family, viroporins may represent a viable target to curb viral infectivity. To this end, using three bacterial assays we analyzed six small hydrophobic proteins from biomedically important viruses as potential viroporin candidates. Our results indicate that Eastern equine encephalitis virus 6k, West Nile virus MgM, Dengue virus 2k, Dengue virus P1, Variola virus gp170, and Variola virus gp151 proteins all exhibit channel activity in the bacterial assays, and as such may be considered viroporin candidates. It is clear that more studies, such as patch clamping, will be needed to characterize the ionic conductivities of these proteins. However, our approach presents a rapid procedure to analyze open reading frames in other viruses, yielding new viroporin candidates for future detailed investigation. Finally, if conductivity is proven vital to their cognate viruses, the bio-assays presented herein afford a simple approach to screen for new channel blockers.

摘要

病毒离子通道蛋白是一类存在于多种包膜病毒中的小疏水性蛋白,能够进行离子转运。基于通过阻断其典型的 M2 H 通道来抑制流感的能力,病毒离子通道蛋白作为一个家族,可能是抑制病毒感染力的一个可行靶点。为此,我们使用三种细菌测定法分析了来自具有重要医学意义的病毒的六种小疏水性蛋白,以确定它们是否可能成为病毒离子通道蛋白候选物。我们的结果表明,东部马脑炎病毒 6k、西尼罗河病毒 MgM、登革热病毒 2k、登革热病毒 P1、天花病毒 gp170 和天花病毒 gp151 蛋白在细菌测定中均表现出通道活性,因此可被视为病毒离子通道蛋白候选物。显然,需要进行更多的研究,例如膜片钳技术,以表征这些蛋白的离子电导率。然而,我们的方法提供了一种快速分析其他病毒开放阅读框的方法,为未来的详细研究提供了新的病毒离子通道蛋白候选物。最后,如果电导率对它们的同源病毒至关重要,本文中提出的生物测定法为筛选新的通道阻断剂提供了一种简单的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b471/6669592/d9e171c24f30/viruses-11-00632-g001.jpg

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