Engineering a live-attenuated porcine reproductive and respiratory syndrome virus vaccine to prevent RNA recombination by rewiring transcriptional regulatory sequences

文献类型： 外文期刊

第一作者： Li, Liwei

作者： Li, Liwei;Chen, Jinxia;Cao, Zhengda;Guo, Ziqiang;Liu, Jiachen;Zhou, Yanjun;Tong, Guangzhi;Gao, Fei;Chen, Jinxia;Tong, Guangzhi;Gao, Fei

作者机构：

关键词： RNA recombination; porcine reproductive and respiratory syndrome virus (PRRSV); transcriptional regulatory sequence (TRS); recombination-resistant; vaccine redesign

期刊名称：MBIO （ 影响因子：4.7； 五年影响因子：5.5 ）

ISSN：

年卷期： 2025 年 16 卷 2 期

页码：

收录情况： SCI

摘要： Recombination is a significant factor driving the evolution of RNA viruses. The prevalence and variation of porcine reproductive and respiratory syndrome virus (PRRSV) in China have been increasing in complexity due to extensive interlineage recombination. When this recombination phenomenon occurs in live vaccine strains, it becomes increasingly difficult to prevent and control PRRSV. Reverse genetic manipulation to engineer a different transcriptional regulatory sequence (TRS) circuit introduces genetic traps into the viral genome that are lethal to recombinant RNA progeny viruses. In this study, major interlineage recombination patterns were identified between lineage 1 (L1) PRRSVs and lineage 8 (L8) PRRSVs in China, from 2019 to 2023. The recombinant mutant virus, vA-TRSall, was constructed and successfully rescued by rewiring the entire TRS circuit without changing the amino acid-coding sequence in the genome of the PRRSV live vaccine strain vHuN4-F112. The vA-TRSall, with a brand new TRS circuit, provided effective immune protection against the highly pathogenic L8 PRRSV (vHuN4) and epidemic NADC30-like L1 PRRSV (vZJqz21). Recombination analysis in vitro and in vivo showed that, compared with the vHuN4-F112 and vZJqz21 co-infection groups, the incidence rates of mutation breakpoints and template-switching recombination in the vA-TRSall and vZJqz21 co-infected groups were effectively reduced. The results have enriched our understanding of the critical role of TRS circuits in PRRSV recombination mechanisms and indicate a successful redesign that can endow PRRSV live vaccines with recombination-resistant capabilities.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序