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

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

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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 patho-genesis 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 neural-attenuated 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 char-acterized 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.

Herpes simplex virus-1(HSV-1)Herpes simplex encephalitis(HSE)ICP34.5NeuroinflammationNeuronal loss

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

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Key Laboratory of Second Affiliated Hospital of Kunming Medical University,Kunming 650000,China

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

Kunming College of Life Science,University of Chinese Academy of Sciences,Kunming 650204,China

Department of Microbiology,Perelman School of Medicine,University of Pennsylvania,Philadelphia,PA,19104,USA

Department of Biology and Immunology,Kunming Medical University,Kunming,650101,China

KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases,Kunming,650223,China

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National Natural Science Foundation of China-Yunnan Joint Found(NSFC)National Natural Science Foundation of China-Yunnan Joint Found(NSFC)National Natural Science Foundation of China(NSFC)National Natural Science Foundation of China(NSFC)National Natural Science Foundation of China(NSFC)Ministry of Science and Technology of China(MOST)Ministry of Science and Technology of China(MOST)Ministry of Science and Technology of China Foreign Expert ProgramCAS"Light of West China"Programa Thousand Foreign Talent scholarship from Yunnan ProvinceHighend Foreign Expert Project of Yunnan Revitalization Talent Support ProgramTechnology Innovation Team of Kunming Medical UniversityInternational Science and Technology Cooperation ProjectYunnan Training Project for Medical Talentsbiomedical Special Project of the Department of Science and Technology of Yunnan ProvinceChinese Academy of Sciences President's International Fellowship Initiative(PIFI)China Postdoctoral Science FoundationMedical reserve Talents Training Program of Yunnan Provincial Health Commission of ChinaYunnan Fundamental Research ProjectsOpen Research Fund

U2202215U1602226816720408206306318020262018YFC20004022018YFE0203700G2021061008Lxbzgzdsys-201909CXTD2018042017IB011L-2017014202102AA100007-42019VBA00452022MD713758H-2019059202201AT070195HXDT-2019-1

2023

中国病毒学
中国科学院武汉病毒研究所，中国微生物学会

中国病毒学

CSTPCDCSCD北大核心
影响因子：0.393
ISSN：1674-0769
年,卷(期)：2023.(1)
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