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Coxsackievirus B3 HFMD Animal models in Syrian hamster and rhesus monkey

Virologica Sinica 2024年第2期39卷 290-300页

作者： Suqin Duan Wei Zhang Yongjie Li Yanyan Li Yuan Zhao Weihua Jin Quan Liu Mingxue Li Wenting Sun Lixiong Chen Hongjie Xu Jie Tang Jinghan Hou Zijun Deng Fengmei Yang Shaohui Ma Zhanlong He Institute of Medical Biology Chinese Academy of Medical Sciences Medical Primate Research Center Peking Union Medical CollegeYunnan Key Laboratory of Vaccine Research Development on Severe Infectious DiseaseKunming650118China

Coxsackievirus B3(CVB3)is the pathogen causing hand,foot and mouth disease(HFMD),which manifests across a spectrum of clinical severity from mild to severe.However,CVB3-infected mouse models mainly demonstrate viral myocarditis and pancreatitis,failing to replicate human HFMD symptoms.Although several enteroviruses have been evaluated in Syrian hamsters and rhesus monkeys,there is no comprehensive data on CVB3.In this study,we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different routes.The results showed that Syrian hamsters were successfully infected with CVB3 by intraperitoneal injection or nasal drip,leading to nasopharyngeal colonization,acute severe pathological injury,and typical HFMD symptoms.Notably,the nasal drip group exhibited a longer viral excretion cycle and more severe pathological damage.In the subsequent study,rhesus monkeys infected with CVB3 through nasal drips also presented signs of HFMD symptoms,viral excretion,serum antibody conversion,viral nucleic acids and antigens,and the specific organ damages,particularly in the heart.Surprisingly,there were no significant differences in myocardial enzyme levels,and the clinical symptoms resembled those often associated with common,mild infections.In summary,the study successfully developed severe Syrian hamsters and mild rhesus monkey models for CVB3-induced HFMD.These models could serve as a basis for understanding the disease pathogenesis,conducting pre-trial prevention and evaluation,and implementing post-exposure intervention.

关键词： Coxsackievirus B3(CVB3) Hand foot and mouth disease(HFMD) Animal models Syrian hamster Rhesus monkey

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SARS-CoV-2 immunity in Animal models

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Cellular & Molecular Immunology 2024年第2期21卷 119-133页

作者： Zhao Chen Yaochang Yuan Qingtao Hu Airu Zhu Fenghua Chen Shu Li Xin Guan Chao Lv Tian Tang Yiyun He Jinling Cheng Jie Zheng Xiaoyu Hu Jingxian Zhao Jincun Zhao Jing Sun State Key Laboratory of Respiratory Disease National Clinical Research Centre for Respiratory DiseaseNational Centre for Respiratory MedicineGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510182China GMU-GIBH Joint School of Life Sciences Guangzhou Medical UniversityGuangzhou 510000China Guangzhou National Laboratory GuangzhouGuangdong 510005China Shanghai Institute for Advanced Immunochemical Studies School of Life Science and TechnologyShanghaiTech UniversityShanghai 201210China Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People’s Hospitalthe Second Affiliated HospitalSchool of MedicineSouthern University of Science and TechnologyShenzhen 518005China

The COVID-19 pandemic,which was caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has become a worldwide health crisis due to its transmissibility.SARS-CoV-2 infection results in severe respiratory illness and can lead to significant complications in affected individuals.These complications encompass symptoms such as coughing,respiratory distress,fever,infectious shock,acute respiratory distress syndrome(ARDS),and even multiple-organ failure.Animal models serve as crucial tools for investigating pathogenic mechanisms,immune responses,immune escape mechanisms,antiviral drug development,and vaccines against SARS-CoV-2.Currently,various Animal models for SARS-CoV-2 infection,such as nonhuman primates(NHPs),ferrets,hamsters,and many different mouse models,have been developed.Each model possesses distinctive features and applications.In this review,we elucidate the immune response elicited by SARS-CoV-2 infection in patients and provide an overview of the characteristics of various Animal models mainly used for SARS-CoV-2 infection,as well as the corresponding immune responses and applications of these models.A comparative analysis of transcriptomic alterations in the lungs from different Animal models revealed that the K18-hACE2 and mouse-adapted virus mouse models exhibited the highest similarity with the deceased COVID-19 patients.Finally,we highlighted the current gaps in related research between animal model studies and clinical investigations,underscoring lingering scientific questions that demand further clarification.

关键词： COVID-19 SARS-CoV-2 Animal models immune response

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Targeting autophagy in Alzheimer's disease:Animal models and mechanisms

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Zoological Research 2023年第6期44卷 1132-1145页

作者： Xiao-Wen Zhang Xiang-Xing Zhu Dong-Sheng Tang Jia-Hong Lu State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoTaipaMacao 99078China Guangdong Provincial Key Laboratory of animal Molecular Design and Precise Breeding Gene Editing Technology Center of Guangdong ProvinceFoshan UniversityFoshanGuangdong 528225China

Alzheimer's disease(AD)is an age-related progressive neurodegenerative disorder that leads to cognitive impairment and memory loss.Emerging evidence suggests that autophagy plays an important role in the pathogenesis of AD through the regulation of amyloid-beta(Aβ)and tau metabolism,and that autophagy dysfunction exacerbates amyloidosis and tau pathology.Therefore,targeting autophagy may be an effective approach for the treatment of AD.Animal models are considered useful tools for investigating the pathogenic mechanisms and therapeutic strategies of diseases.This review aims to summarize the pathological alterations in autophagy in representative AD Animal models and to present recent studies on newly discovered autophagy-stimulating interventions in animal AD models.Finally,the opportunities,difficulties,and future directions of autophagy targeting in AD therapy are discussed.

关键词： Alzheimer's disease Aβmetabolism Tau pathology Autophagy Animal models

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Application of Animal models to compare and contrast the virulence of current and future potential SARS-CoV-2 variants

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Biosafety and Health 2022年第3期4卷 154-160页

作者： Zhe Ding Tong Chen Jiaming Lan Gary Wong Viral Hemorrhagic Fevers Research Unit CAS Key Laboratory of Molecular Virology and ImmunologyInstitut Pasteur of ShanghaiChinese Academy of SciencesShanghai 200031China University of Chinese Academy of Sciences Beijing 100190China

Since severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)was first identified during late 2019,the sustained spread of this pathogen within the human population has caused worldwide disruption with staggering infection rates and death tolls.Due to the accumulation of mutations in SARS‐CoV‐2,the virus has evolved into many variants,five of which have been listed as variants of concern VOCs by the World Health Organization(WHO).Multiple Animal models of SARS‐CoV‐2 have been developed to evaluate vaccines and drugs and to assess the pathogenicity,transmissibility and antiviral measures of these VOCs.Here,we review the cutting‐edge research based on mouse,hamster,ferret and non‐human primate models for evaluating SARS‐CoV‐2 with a focus on the Omicron variant,and highlight the importance of updating vaccines in a timely manner in order to mitigate the negative effects of SARS‐CoV‐2 infections in the human population.

关键词： SARS‐CoV‐2 Animal models Variants of concern Omicron

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Animal models in the study of Alzheimer's disease and Parkinson's disease:A historical perspective

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Animal models and Experimental Medicine 2022年第1期5卷 27-37页

作者： Rajashree Banerjee Arushi Rai Shreyas M.Iyer Sonia Narwal Meghana Tare Department of Biological Sciences Birla Institute of Technology and SciencePilaniIndia

Alzheimer's disease and Parkinson's disease are two of the most prevalent and disabling neurodegenerative diseases globally.Both are proteinopathic conditions and while occasionally inherited,are largely sporadic in nature.Although the advances in our understanding of the two have been significant,they are far from complete and neither diagnosis nor the current practices in treatment and rehabilitation is adequately helpful.Animal models have historically found application as testing beds for novel therapeutics and continue to be valuable aids in pharmacological research.This review chronicles the development of those models in the context of Alzheimer's and Parkinson's disease,and highlights the shifting paradigms in studying two humanspecific conditions in non-human organisms.

关键词： Alzheimer's disease Animal models neurodegeneration Parkinson's disease

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Experimental Animal models of pulmonary hypertension:Development and challenges

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Animal models and Experimental Medicine 2022年第3期5卷 207-216页

作者： Xiao-Han Wu Jie-Ling Ma Dong Ding Yue-Jiao Ma Yun-Peng Wei Zhi-Cheng Jing Department of Cardiology State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Medical Science Research Center State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Pulmonary hypertension(PH) is clinically divided into 5 major types, characterized by elevation in pulmonary arterial pressure(PAP) and pulmonary vascular resistance(PVR), finally leading to right heart failure and death. The pathogenesis of this arteriopathy remains unclear, leaving it impossible to target pulmonary vascular remodeling and reverse the deterioration of right ventricular(RV) function. Different Animal models have been designed to reflect the complex mechanistic origins and pathology of PH, roughly divided into 4 categories according to the modeling methods: noninvasive models in vivo, invasive models in vivo, gene editing models, and multi-means joint modeling. Though each model shares some molecular and pathological changes with different classes of human PH, in most cases the molecular etiology of human PH is poorly known. The appropriate use of classic and novel PH Animal models is essential for the hunt of molecular targets to reverse severe phenotypes.

关键词： Animal models BMPR2 chronic hypoxia monocrotaline pulmonary hypertension Sugen 5416

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Understanding autism spectrum disorders with Animal models:applications,insights,and perspectives

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Zoological Research 2021年第6期42卷 800-824页

作者： Zhu Li Yuan-Xiang Zhu Li-Jun Gu Ying Cheng Institute of Biomedical Research Yunnan UniversityKunmingYunnan 650500China

Autism spectrum disorder(ASD)is typically characterized by common deficits in social skills and repetitive/stereotyped behaviors.It is widely accepted that genetic and environmental factors solely or in combination cause ASD.However,the underlying pathogenic mechanism is unclear due to its highly heterogeneous nature.To better understand the pathogenesis of ASD,various Animal models have been generated,which can be generally divided into genetic,environment-induced,and idiopathic Animal models.In this review,we summarize the common animals used for ASD study and then discuss the applications,clinical insights,as well as challenges and prospects of current ASD Animal models.

关键词： Autism spectrum disorders Animal models Neurodevelopment Genetics Environment

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Breast cancer Animal models and applications

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Zoological Research 2020年第5期41卷 477-494页

作者： Li Zeng Wei Li Ce-Shi Chen Key Laboratory of Animal models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Kunming College of Life Science University of the Chinese Academy of SciencesKunmingYunnan 650204China KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China

Breast cancer is the most common malignancy in women. Basic and translational breast cancer research relies heavily on experimental Animal models. Ideally, such models for breast cancer should have commonality with human breast cancer in terms of tumor etiology, biological behavior,pathology, and response to therapeutics. This review introduces current progress in different breast cancer experimental Animal models and analyzes their characteristics, advantages, disadvantages, and potential applications. Finally, we propose future research directions for breast cancer Animal models.

关键词： Breast cancer Animal models Metastasis Drug development

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Protective effects of pharmacological therapies in Animal models of multiple sclerosis: a review of studies 2014–2019

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Neural Regeneration Research 2020年第7期15卷 1220-1234页

作者： Bridget Martinez Philip V.Peplow Physical Chemistry and Applied Spectroscopy Chemistry DivisionLos Alamos National LaboratoryLos AlamosNMUSA Department of Medicine St.Georges University School of MedicineTrue BlueGrenada Department of Anatomy University of OtagoDunedinNew Zealand

Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous system.The disability caused by inflammatory demyelination clinically dominates the early stages of relapsing-remitting MS and is reversible.Once there is considerable loss of axons,MS patients enter a secondary progressive stage.Disease-modifying drugs currently in use for MS suppress the immune system and reduce relapse rates but are not effective in the progressive stage.Various Animal models of MS(mostly mouse and rat)have been established and proved useful in studying the disease process and response to therapy.The experimental autoimmune encephalomyelitis animal studies reviewed here showed that a chronic progressive disease can be induced by immunization with appropriate amounts of myelin oligodendrocyte glycoprotein together with mycobacterium tuberculosis and pertussis toxin in Freund's adjuvant.The clinical manifestations of autoimmune encephalomyelitis disease were prevented or reduced by treatment with certain pharmacological agents given prior to,at,or after peak disease,and the agents had protective effects as shown by inhibiting demyelination and damage to neurons,axons and oligodendrocytes.In the cuprizone-induced toxicity animal studies,the pharmacological agents tested were able to promote remyelination and increase the number of oligodendrocytes when administered therapeutically or prophylactically.A monoclonal IgM antibody protected axons in the spinal cord and preserved motor function in animals inoculated with Theiler's murine encephalomyelitis virus.In all these studies the pharmacological agents were administered singly.A combination therapy may be more effective,especially using agents that target neuroinflammation and neurodegeneration,as they may exert synergistic actions.

关键词： Animal models autoimmune encephalomyelitis disease cuprizone-induced toxicity multiple sclerosis neurodegeneration neuroinflammation neuroprotection pharmacological agents progressive disease Theiler's murine encephalomyelitis virus

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Animal models of stroke

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Animal models and Experimental Medicine 2021年第3期4卷 204-219页

作者： Yanyu Li Jingjing Zhang Affiliated Hospital of Guangdong Medical University&Key Laboratory of Zebrafish Model for Development and Diseases of Guangdong Medical University ZhanjiangChina

Stroke is a devastating disease with high morbidity and mortality.Animal models are indispensable tools that can mimic stroke processes and can be used for investigating mechanisms and developing novel therapeutic regimens.As a heterogeneous disease with complex pathophysiology,mimicking all aspects of human stroke in one animal model is impossible.Each model has unique strengths and weaknesses.models such as transient or permanent intraluminal thread occlusion middle cerebral artery oc-clusion(MCAo)models and thromboembolic models are the most commonly used in simulating human ischemic stroke.The endovascular filament occlusion model is characterized by easy manipulation and accurately controllable reperfusion and is suitable for studying the pathogenesis of focal ischemic stroke and reperfusion in-jury.Although the reproducibility of the embolic model is poor,it is more conveni-ent for investigating thrombolysis.Rats are the most frequently used animal model for stroke.This review mainly outlines the stroke models of rats and discusses their strengths and shortcomings in detail.

关键词： Animal models cerebral hemorrhage ischemia stroke

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