美国加州大学Raul Andino研究小组取得一项新突破。他们发现缺陷病毒基因组(DVG)可引发对广泛呼吸道病毒的保护性免疫。相关论文发表在2021年11月17日出版的《细胞》杂志上。
为了探究具有缺陷基因组病毒的治疗潜力，研究人员通过删除脊髓灰质炎病毒的衣壳编码区来产生DVG。将该基因组运用于腹膜内或鼻内（研究人员称为eTIP1）可引发抗病毒反应，抑制复制并保护小鼠免受多种RNA病毒的侵害，包括肠道病毒、流感和SARS-CoV-2。虽然鼻内给药后的eTIP1的复制仅限于鼻腔，但其抗病毒作用可通过非细胞方式自主地扩展到肺部。eTIP1的广谱抗病毒作用由局部和远端I型干扰素反应介导。
重要的是，虽然eTIP1单剂量可以保护动物免受SARS-CoV-2感染，但它也会刺激SARS-CoV-2中和抗体的产生，从而为SARS-CoV-2再感染提供长期保护。因此，eTIP1是一种安全有效的广谱抗病毒药物，可在动物模型中发挥对SARS-CoV-2和其他呼吸道感染的短期和长期保护作用。
据悉，RNA 病毒产生DVG，可干扰野生型亲本病毒的复制。
附：英文原文
Title: A defective viral genome strategy elicits broad protective immunity against respiratory viruses
Author: Yinghong Xiao, Peter V. Lidsky, Yuta Shirogane, Ranen Aviner, Chien-Ting Wu, Weiyi Li, Weihao Zheng, Dale Talbot, Adam Catching, Gilad Doitsh, Weiheng Su, Colby E. Gekko, Arabinda Nayak, Joel D. Ernst, Leonid Brodsky, Elia Brodsky, Elsa Rousseau, Sara Capponi, Simone Bianco, Robert Nakamura, Peter K. Jackson, Judith Frydman, Raul Andino
Issue&Volume: 2021-11-17
Abstract: RNA viruses generate defective viral genomes (DVG) that can interfere with replication of the parental wild-type virus. To examine their therapeutic potential, we created a DVG by deleting the capsid-coding region of poliovirus. Strikingly, intraperitoneal or intranasal administration of this genome, which we termed eTIP1, elicits an antiviral response, inhibits replication and protects mice from several RNA viruses, including enteroviruses, influenza and SARS-CoV-2. While eTIP1 replication following intranasal administration is limited to the nasal cavity, its antiviral action extends non-cell-autonomously to the lungs. eTIP1 broad-spectrum antiviral effects are mediated by both local and distal type I interferon responses. Importantly, while a single eTIP1 dose protects animals from SARS-CoV-2 infection, it also stimulates production of SARS-CoV-2 neutralizing antibodies that afford long-lasting protection from SARS-CoV-2 reinfection. Thus, eTIP1 is a safe and effective broad-spectrum antiviral generating short- and long-term protection against SARS-CoV-2 and other respiratory infections in animal models.
DOI: 10.1016/j.cell.2021.11.023
Source: https://www.cell.com/cell/fulltext/S0092-8674(21)01338-6