Human enterovirus A71(EV-A71)is a major causative agent of hand,foot and mouth disease(HFMD),which poses a significant public health threat,particularly among young children.Mitochondrial antiviral signaling protein(M...Human enterovirus A71(EV-A71)is a major causative agent of hand,foot and mouth disease(HFMD),which poses a significant public health threat,particularly among young children.Mitochondrial antiviral signaling protein(MAVS)and interferon regulatory factor 3(IRF3)are vital proteins for the induction of type I interferons(IFN-I)and downstream interferon-stimulated genes(ISGs)during EVA71 infection.While posttranslational modifications are known to critically influence viral infection processes,the mechanisms by which EV-A71 exploits host deubiquitinases(DUBs)for immune evasion remain poorly understood.In this study,we demonstrated that EV-A71 infection upregulated ubiquitinspecific protease 5(USP5)expression.Knockdown of USP5 not only inhibited EV-A71 replication but also observably increased the production of IFN-I and ISGs.Furthermore,USP5 also regulated the replication of EV-D68 and CVA16 and the production of IFN-I and ISGs.Mechanistically,USP5 physically interacted with MAVS and IRF3 and reduced the K63-linked polyubiquitination of MAVS and IRF3.Conversely,USP5 knockdown increased the K63-linked polyubiquitination of MAVS and IRF3,thereby accelerating the phosphorylation of IRF3 and increasing IFN-I production during EV-A71 infection.Furthermore,pharmacological inhibition of USP5 with the small-molecule inhibitor PR-619 significantly potentiated the antiviral effects of IFN against EV-A71.Collectively,our findings reveal a previously unrecognized role of USP5 in facilitating EV-A71 immune evasion by dampening MAVSand IRF3-mediated antiviral signaling.These insights provide a novel therapeutic avenue for combating EV-A71 infection through targeted modulation of the USP5-IRF3 axis.展开更多
配置MIMU(Micro Inertial Measurement Unit,微惯性测量单元)中的加速度计工作在倾角仪状态,利用当地的重力加速度计算MAV(Micro Air Vehicles,微小型飞行器)的姿态角。同时利用MIMU中的陀螺仪,计算载体的姿态角。提出了一种构造加权系...配置MIMU(Micro Inertial Measurement Unit,微惯性测量单元)中的加速度计工作在倾角仪状态,利用当地的重力加速度计算MAV(Micro Air Vehicles,微小型飞行器)的姿态角。同时利用MIMU中的陀螺仪,计算载体的姿态角。提出了一种构造加权系数的方法,可以根据MIMU的特性,构造不同性能的加权系数。通过对姿态角进行加权平均,实现惯性数据的融合,对MAV的姿态进行估计。该方法既保证了飞行器稳定飞行时姿态估计的精度,避免了姿态误差随时间的积累;又保证了姿态估计系统的动态性能,减小了系统的动态误差。基于该方法搭建的微小型AHRS(Attitude and Heading Reference System,姿态航向参考系统)体积小、重量轻、精度高,特别适用于载荷与体积都有限的载体使用。展开更多
基金supported by the National Natural Science Foundation of China(32300133 to SZ.and 32100106 to YR)the China Postdoctoral Science Foundation(2023M730965 to SZ.)+3 种基金the Science and Technology Department of Henan Province(232102311103 to SZ.)the Chinese Academy of Sciences(CAS)Youth Innovation Promotion Association(2023351 to YR)the Hubei Province Natural Science Funds(2023AFA008 and 2023AFB582 to YR)the Open project of the State Key Laboratory of Antiviral Drugs,Henan University(FX3020A030002).
文摘Human enterovirus A71(EV-A71)is a major causative agent of hand,foot and mouth disease(HFMD),which poses a significant public health threat,particularly among young children.Mitochondrial antiviral signaling protein(MAVS)and interferon regulatory factor 3(IRF3)are vital proteins for the induction of type I interferons(IFN-I)and downstream interferon-stimulated genes(ISGs)during EVA71 infection.While posttranslational modifications are known to critically influence viral infection processes,the mechanisms by which EV-A71 exploits host deubiquitinases(DUBs)for immune evasion remain poorly understood.In this study,we demonstrated that EV-A71 infection upregulated ubiquitinspecific protease 5(USP5)expression.Knockdown of USP5 not only inhibited EV-A71 replication but also observably increased the production of IFN-I and ISGs.Furthermore,USP5 also regulated the replication of EV-D68 and CVA16 and the production of IFN-I and ISGs.Mechanistically,USP5 physically interacted with MAVS and IRF3 and reduced the K63-linked polyubiquitination of MAVS and IRF3.Conversely,USP5 knockdown increased the K63-linked polyubiquitination of MAVS and IRF3,thereby accelerating the phosphorylation of IRF3 and increasing IFN-I production during EV-A71 infection.Furthermore,pharmacological inhibition of USP5 with the small-molecule inhibitor PR-619 significantly potentiated the antiviral effects of IFN against EV-A71.Collectively,our findings reveal a previously unrecognized role of USP5 in facilitating EV-A71 immune evasion by dampening MAVSand IRF3-mediated antiviral signaling.These insights provide a novel therapeutic avenue for combating EV-A71 infection through targeted modulation of the USP5-IRF3 axis.
文摘配置MIMU(Micro Inertial Measurement Unit,微惯性测量单元)中的加速度计工作在倾角仪状态,利用当地的重力加速度计算MAV(Micro Air Vehicles,微小型飞行器)的姿态角。同时利用MIMU中的陀螺仪,计算载体的姿态角。提出了一种构造加权系数的方法,可以根据MIMU的特性,构造不同性能的加权系数。通过对姿态角进行加权平均,实现惯性数据的融合,对MAV的姿态进行估计。该方法既保证了飞行器稳定飞行时姿态估计的精度,避免了姿态误差随时间的积累;又保证了姿态估计系统的动态性能,减小了系统的动态误差。基于该方法搭建的微小型AHRS(Attitude and Heading Reference System,姿态航向参考系统)体积小、重量轻、精度高,特别适用于载荷与体积都有限的载体使用。
