Persistent inflammation and neuronal loss in the mouse brain induced by a modified form of attenuated herpes simplex virus type I  

作　　者：Erlin Wang Xinwei Huang Yunshuang Ye Shiqing Zou Guijun Chen Liping Yang Nigel W.Fraser Fukai Bao Jumin Zhou Xia Cao 

机构地区：[1]Key Laboratory of Second Affiliated Hospital of Kunming Medical University,Kunming,650000,China [2]Key Laboratory of Animal Models and Human Disease Mechanism of the Chinese Academy of Science/Key Laboratory of Healthy Aging Research of Yunnan Province,Kunming Institute of Zoology,The Chinese Academy of Sciences,Kunming,650223,China [3]Kunming College of Life Science,University of Chinese Academy of Sciences,Kunming,650204,China [4]Department of Microbiology,Perelman School of Medicine,University of Pennsylvania,Philadelphia,PA,19104,USA [5]Department of Biology and Immunology,Kunming Medical University,Kunming,650101,China [6]KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases,Kunming,650223,China

出　　处：《Virologica Sinica》2023年第1期108-118,共11页中国病毒学（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China-Yunnan Joint Found(NSFC,U2202215,U1602226);the National Natural Science Foundation of China(NSFC,81672040 to J.Zhou,8206306 to X.Cao,and 31802026 to L.Li);the Ministry of Science and Technology of China(MOST,2018YFC2000402,2018YFE0203700);the Ministry of Science and Technology of China Foreign Expert Program to J.Zhou(G2021061008L);the CAS“Light of West China”Program(xbzg-zdsys-201909)to J.Zhou,a Thousand Foreign Talent scholarship from Yunnan Province and High-end Foreign Expert Project of Yunnan Revitalization Talent Support Program to J.Zhou;the Technology Innovation Team of Kunming Medical University(CXTD201804);the International Science and Technology Cooperation Project(2017IB011);the Yunnan Training Project for Medical Talents(L-2017014);the biomedical Special Project of the Department of Science and Technology of Yunnan Province(202102AA100007-4)to X.Cao;the Chinese Academy of Sciences President's International Fellowship Initiative(PIFI,2019VBA0045)to N.W.Fraser;the China Postdoctoral Science Foundation(2022MD713758)to E.Wang;the Medical reserve Talents Training Program of Yunnan Provincial Health Commission of China(H-2019059)to X.Huang;the Yunnan Fundamental Research Projects(202201AT070195)to Y.Ye.;Open Research Fund HXDT-2019-1 to J.Zhou.

摘　　要：Herpes simplex virus-1(HSV-1)is a widespread neurotropic virus that can reach the brain and cause a rare but acute herpes simplex encephalitis(HSE)with a high mortality rate.Most patients present with changes in neurological and behavioral status,and survivors suffer long-term neurological sequelae.To date,the pathogenesis leading to brain damage is still not well understood.HSV-1 induced encephalitis in the central nervous system(CNS)in animals are usually very diffuse and progressing rapidly,and mostly fatal,making the analysis difficult.Here,we established a mouse model of HSE via intracerebral inoculation of modified version of neuralattenuated strains of HSV-1(deletion of ICP34.5 and inserting a strong promoter into the latency-associated transcript region),in which the LMR-αΔpA strain initiated moderate productive infection,leading to strong host immune and inflammatory response characterized by persistent microglia activation.This viral replication activity and prolonged inflammatory response activated signaling pathways in neuronal damage,amyloidosis,Alzheimer's disease,and neurodegeneration,eventually leading to neuronal loss and behavioral changes characterized by hypokinesia.Our study reveals detailed pathogenic processes and persistent inflammatory responses in the CNS and provides a controlled,mild and non-lethal HSE model for studying long-term neuronal injury and increased risk of neurodegenerative diseases due to HSV-1 infection.

关 键 词：Herpes simplex virus-1(HSV-1) Herpes simplex encephalitis(HSE) ICP34.5 NEUROINFLAMMATION Neuronal loss 

分 类 号：R373[医药卫生—病原生物学]