近日,瑞士苏黎世联邦理工学院Donald Hilvert及其小组实现类病毒架构和包装机制的演化。相关论文于2021年6月11日发表在《科学》杂志上。
研究人员表示,病毒是影响全球的病原体。
受一种假说的提示,即它们最早的祖先招募宿主蛋白质用于病毒粒子形成,研究人员使用严格的实验室进化将一种对核酸缺乏亲和力的细菌酶转化为人工核衣壳,该核衣壳有效地包装和保护其自身编码信使RNA的多个副本。
通过揭示天然病毒分子特征的显著趋同,随之而来的变化将蛋白质构建块重新组织成一个交错的240个亚基构成的二十面体衣壳,它对核酸酶是不可穿透的,而强大的RNA茎环包装框架的出现确保了高的衣壳化产量和特异性。除了证明原始病毒的合理进化途径外,这些发现还强调了为各种疫苗和递送应用开发非病毒载体的实用策略。
附:英文原文
Title: Evolution of a virus-like architecture and packaging mechanism in a repurposed bacterial protein
Author: Stephan Tetter, Naohiro Terasaka, Angela Steinauer, Richard J. Bingham, Sam Clark, Andrew J. P. Scott, Nikesh Patel, Marc Leibundgut, Emma Wroblewski, Nenad Ban, Peter G. Stockley, Reidun Twarock, Donald Hilvert
Issue&Volume: 2021/06/11
Abstract: Viruses are ubiquitous pathogens of global impact. Prompted by the hypothesis that their earliest progenitors recruited host proteins for virion formation, we have used stringent laboratory evolution to convert a bacterial enzyme that lacks affinity for nucleic acids into an artificial nucleocapsid that efficiently packages and protects multiple copies of its own encoding messenger RNA. Revealing remarkable convergence on the molecular hallmarks of natural viruses, the accompanying changes reorganized the protein building blocks into an interlaced 240-subunit icosahedral capsid that is impermeable to nucleases, and emergence of a robust RNA stem-loop packaging cassette ensured high encapsidation yields and specificity. In addition to evincing a plausible evolutionary pathway for primordial viruses, these findings highlight practical strategies for developing nonviral carriers for diverse vaccine and delivery applications.
DOI: 10.1126/science.abg2822
Source: https://science.sciencemag.org/content/372/6547/1220