冠状病毒内切核糖核酸酶(EndoU)nsp15在通过减少病毒双链RNA(dsRNA)含量以逃避免疫系统识别方面发挥关键作用。然而,关于它与宿主细胞靶标之间的相互作用仍知之甚少。2025年3月17日,中国农业科学院上海兽医研究所廖瑛研究员带领的科研...冠状病毒内切核糖核酸酶(EndoU)nsp15在通过减少病毒双链RNA(dsRNA)含量以逃避免疫系统识别方面发挥关键作用。然而,关于它与宿主细胞靶标之间的相互作用仍知之甚少。2025年3月17日,中国农业科学院上海兽医研究所廖瑛研究员带领的科研团队在国际期刊PLoS Pathogens上发表了题为“Coronavirus endoribonuclease nsp15 suppresses host protein synthesis and evades PKR-eIF2α-mediated translation shutoff to ensure viral protein synthesis”的研究论文,揭示了nsp15 EndoU酶活性在蛋白合成关闭中的独特且保守的作用机制,深化了人们对冠状病毒调控宿主蛋白表达策略的理解。展开更多
The evolution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in mutations not only in the spike protein,aiding immune evasion,but also in the NSP3/4/6 proteins,crucial for regulating double...The evolution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in mutations not only in the spike protein,aiding immune evasion,but also in the NSP3/4/6 proteins,crucial for regulating double-membrane vesicle(DMV)formation.However,the functional consequences of these NSP3/4/6 mutations remain poorly understood.In this study,a systematic analysis was conducted to investigate the evolutionary patterns of NSP3/4/6 mutations and their impact on DMV formation.The findings revealed that the NSP4 T492I mutation,a prevalent mutation found in all Delta and Omicron sub-lineages,notably enhances DMV formation.Mechanistically,the NSP4 T492I mutation enhances its homodimerization,leading to an increase in the size of puncta induced by NSP3/4,and also augments endoplasmic reticulum(ER)membrane curvature,resulting in a higher DMV density per fluorescent puncta.This study underscores the significance of the NSP4 T492I mutation in modulating DMV formation,with potential implications for the transmission dynamics of SARS-CoV-2.It contributes valuable insights into how these mutations impact viral replication and pathogenesis.展开更多
文摘冠状病毒内切核糖核酸酶(EndoU)nsp15在通过减少病毒双链RNA(dsRNA)含量以逃避免疫系统识别方面发挥关键作用。然而,关于它与宿主细胞靶标之间的相互作用仍知之甚少。2025年3月17日,中国农业科学院上海兽医研究所廖瑛研究员带领的科研团队在国际期刊PLoS Pathogens上发表了题为“Coronavirus endoribonuclease nsp15 suppresses host protein synthesis and evades PKR-eIF2α-mediated translation shutoff to ensure viral protein synthesis”的研究论文,揭示了nsp15 EndoU酶活性在蛋白合成关闭中的独特且保守的作用机制,深化了人们对冠状病毒调控宿主蛋白表达策略的理解。
基金supported by the National Natural Science Foundation of China(92469107 to Z.Li)the R&D Program of Guangzhou National Laboratory(ZL-SRPG2200205 to Z.Li)the Guangdong Province High-level Talent Youth Project(2021QN02Y939 to Z.Li).
文摘The evolution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in mutations not only in the spike protein,aiding immune evasion,but also in the NSP3/4/6 proteins,crucial for regulating double-membrane vesicle(DMV)formation.However,the functional consequences of these NSP3/4/6 mutations remain poorly understood.In this study,a systematic analysis was conducted to investigate the evolutionary patterns of NSP3/4/6 mutations and their impact on DMV formation.The findings revealed that the NSP4 T492I mutation,a prevalent mutation found in all Delta and Omicron sub-lineages,notably enhances DMV formation.Mechanistically,the NSP4 T492I mutation enhances its homodimerization,leading to an increase in the size of puncta induced by NSP3/4,and also augments endoplasmic reticulum(ER)membrane curvature,resulting in a higher DMV density per fluorescent puncta.This study underscores the significance of the NSP4 T492I mutation in modulating DMV formation,with potential implications for the transmission dynamics of SARS-CoV-2.It contributes valuable insights into how these mutations impact viral replication and pathogenesis.
