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科学家开发出一种SARS-CoV-2研究可用的反式互补系统
作者:小柯机器人 发布时间:2021/2/25 15:50:36

美国德克萨斯大学Pei-Yong Shi、Xuping Xie等研究人员合作开发出一种SARS-CoV-2研究可用的反式互补系统,可重现真实的病毒复制但没有任何毒性。这一研究成果于2021年2月23日在线发表在国际学术期刊《细胞》上。

研究人员报告了一个反式互补系统,该系统产生单轮传染性SARS-CoV-2,并概括了真实的病毒复制。研究人员证明,单轮传染性SARS-CoV-2可以在生物安全等级2(BSL-2)实验室用于高通量中和和抗病毒测试。反式互补系统由两个部分组成:包含ORF3和包膜基因缺失以及突变的转录调节序列的基因组病毒RNA,以及表达两个缺失基因的生产细胞系。

这两个成分的反式互补产生的病毒粒子只能感染一次细胞,但不会产生野生型SARS-CoV-2。接种补体衍生病毒粒子的仓鼠和K18-hACE2转基因小鼠即使在颅内接种最高剂量后也未表现出可检测的疾病。因此,反式互补平台可以在BSL-2实验室安全地用于研究和对策开发。 

据悉,培养SARS-CoV-2需要生物安全等级3(BSL-3)的实验室,这是研究的一个瓶颈。

附:英文原文

Title: A trans-complementation system for SARS-CoV-2 recapitulates authentic viral replication without virulence

Author: Xianwen Zhang, Yang Liu, Jianying Liu, Adam L. Bailey, Kenneth S. Plante, Jessica A. Plante, Jing Zou, Hongjie Xia, Nathen E. Bopp, Patricia V. Aguilar, Ping Ren, Vineet D. Menachery, Michael S. Diamond, Scott C. Weaver, Xuping Xie, Pei-Yong Shi

Issue&Volume: 2021-02-23

Abstract: The biosafety level-3 (BSL-3) requirement to culture severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a bottleneck for research. Here we report a trans-complementation system that produces single-round infectious SARS-CoV-2 that recapitulates authentic viral replication. We demonstrate that the single-round infectious SARS-CoV-2 can be used at BSL-2 laboratories for high-throughput neutralization and antiviral testing. The trans-complementation system consists of two components: a genomic viral RNA containing ORF3 and envelope gene deletions as well as mutated transcriptional regulator sequences, and a producer cell line expressing the two deleted genes. Trans-complementation of the two components generates virions that can infect naive cells for only one round, but does not produce wild-type SARS-CoV-2. Hamsters and K18-hACE2 transgenic mice inoculated with the complementation-derived virions exhibited no detectable disease, even after intracranial inoculation with the highest possible dose. Thus, the trans-complementation platform can be safely used at BSL-2 laboratories for research and countermeasure development.

DOI: 10.1016/j.cell.2021.02.044

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00233-6

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/