IL1R1基因敲除对于柯萨奇病毒A10感染C57BL/6乳鼠的影响

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中文摘要：本研究通过柯萨奇病毒A组10型(Coxsackievirus A10,CV-A10)感染C57BL/6野生型乳鼠和白细胞介素-1受体1型(Interleukin 1 Receptor 1,IL-1R1)缺失的C57BL/6乳鼠,比较两者之间的临床症状、病毒体内增殖特征和病理特征差异,以探讨IL-1R1基因缺失对于CV-A10感染乳鼠的影响.本研究采用颅内方式感染C57BL/6野生型和IL-1R1-/-乳鼠,每日记录乳鼠临床症状及死亡情况;两组乳鼠感染后于1、3、5、7、9d处死,并采集各组织样本.通过实时荧光定量 PCR(Real-time reverse transcription-quantitative polymerase chain reaction,RT-qPCR)检测组织内病毒基因拷贝数;使用HE染色检测乳鼠组织的病理学变化;RT-qPCR检测病毒感染乳鼠后的不同时间点组织内的细胞因子mRNA转录水平;利用免疫荧光分析对IFN-γ、IL-1β、IL10的细胞因子表达进行分析.结果发现相比于空白对照组,随着感染进程的增加,两组乳鼠均表现出发育迟缓、肢体麻痹等症状;另外在感染后第5d,与野生型乳鼠相比,IL-1R1-/-乳鼠心脏、肺脏和肾脏组织的CV-A10病毒载量均高于野生型乳鼠,且差异具有统计学意义;通过HE染色分析发现,在感染后期IL-1R1-/-乳鼠的肺组织病变严重程度高于同时期野生型乳鼠.在CV-A10感染中后期IL-1R1-/乳鼠的细胞因子mRNA转录水平明显升高,然而野生型乳鼠的细胞因子mRNA主要在感染后1-2天呈现一过性增加.综上表明,C57BL/6野生型和IL-1R1/-乳鼠均对CV-A10病毒易感;与野生型乳鼠相比,IL-1R1-/-乳鼠的组织损伤更严重,特别是肺组织的损伤主要发生在CV-A10病毒感染的中晚期;此外,IL-1R1缺陷小鼠在感染后期的各组织器官中检测到持续性的细胞因子表达.

外文标题：Influence of IL1R1 Knockout on Coxsackievirus-A10 Infected C57BL/6 Mice

外文摘要：This study compared differences in the clinical features,viral proliferative dynamics and pathological characteristics between coxsackievirus(CV)-A10-infected C57BL/6 wild-type suckling mice and CV-A10-infected interleukin 1 receptor 1(IL-1R1)-deficient suckling mice.We investigated the influence of IL1R1 deletion on CV-A10-infected suckling mice.C57BL/6 wild-type and IL-1R1-/-lactating mice were infected intracranially.The clinical symptoms and mortality of newborn mice were recorded daily.The two groups of newborn mice were sacrificed on 1,3,5,7 and 9 days after infection,and samples of various tissues were collected.The viral gene copies of different tissues were detected by real-time reverse transcription-quantitative polymerase chain reaction(RT-qPCR).Staining(hematoxylin and eosin)was used to detect pathologic changes in different tissues of suckling mice.Cytokine transcription levels in tissues were measured by real-time RT-qPCR.Immunofluorescence staining was used to measure expression of the cytokines interferon-γ,interleukin(IL)-1β and IL10.Compared with the blank control group,suckling mice of both groups showed developmental delay and limb paralysis during infection.The viral loads of IL-1R1-/-suckling mice were higher than those of wild-type suckling mice.The difference in viral load between the two groups was significant in heart,lung and kidney tissue 5 days post-infection.Histopathology showed that lesion severity in IL-1R1-/-suckling mice in the late stage of infection was higher than that in wild-type suckling mice at the same time.mRNA transcription of cytokines of IL-1R1-/-newborn mice was increased in the middle and late stages of CV-A10 infection,but mRNA transcription of wild-type mice increased transiently 1-2 days after CV-A10 infection.Therefore,C57BL/6 wild type and IL-1R1-/-lactating mice were susceptible to CV-A10.Compared with wild-type mice,inflammatory-tissue injuries of IL-1R1-/-lactating mice occurred mainly in the middle and late stages of CV-A10 infection,and CV-A10-infected IL-1R1-/-suckling mice exhibited delayed cytokine production.Transcriptional expression of cytokines was higher and longer than that in wild-type mice in the late stage of CV-A10 infection.

外文关键词：

Coxsackievirus A10Viral infectionIL-1R1-/-suckling miceC57BL/6 Wild-type mice

作者：

刘长坤、贺雅娜、张子寒、胡云光、郑惠文、刘龙丁

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作者单位：

中国医学科学院北京协和医学院医学生物学研究所,昆明 650118

昆明医科大学,昆明 650500

中国医学科学院病毒疫苗研发系统创新研究重点实验室,昆明 650118

关键词：

柯萨奇病毒A10 病毒感染 IL-1R1-/-乳鼠 C57BL/6乳鼠

基金：

云南省科技人才与平台计划中青年学术和技术带头人后备人才项目云南省科技计划-基础研究专项昆明市春城计划春城科技领军人才项目云南省科技计划～生物医药专项

项目编号：

202305AC160008202401AS0700472022SCP010202102AA310043

出版年：

2024

DOI：

10.13242/j.cnki.bingduxuebao.004467

病毒学报

中国微生物学会

病毒学报

CSTPCD北大核心

影响因子：1.046

ISSN：1000-8721

年,卷(期)：2024.40(2)

参考文献量22