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先天性巨细胞病毒感染的啮齿动物模型。

Rodent Models of Congenital Cytomegalovirus Infection.

机构信息

Department for Histology and Embryology and Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.

Department of Infectious Diseases, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.

出版信息

Methods Mol Biol. 2021;2244:365-401. doi: 10.1007/978-1-0716-1111-1_18.

Abstract

Human cytomegalovirus (HCMV) is a leading viral cause of congenital infections in the central nervous system (CNS) and may result in severe long-term sequelae. High rates of sequelae following congenital HCMV infection and insufficient antiviral therapy in the perinatal period makes the development of an HCMV-specific vaccine a high priority of modern medicine. Due to the species specificity of HCMV, animal models are frequently used to study CMV pathogenesis. Studies of murine cytomegalovirus (MCMV) infections of adult mice have played a significant role as a model of CMV biology and pathogenesis, while MCMV infection of newborn mice has been successfully used as a model of perinatal CMV infection. Newborn mice infected with MCMV have high levels of viremia during which the virus establishes a productive infection in most organs, coupled with a robust inflammatory response. Productive infection in the brain parenchyma during early postnatal period leads to an extensive nonnecrotizing multifocal widespread encephalitis characterized by infiltration of components of both innate and adaptive immunity. As a result, impairment in postnatal development of mouse cerebellum leads to long-term motor and sensor disabilities. This chapter summarizes current findings of rodent models of perinatal CMV infection and describes methods for analysis of perinatal MCMV infection in newborn mice.

摘要

人巨细胞病毒(HCMV)是中枢神经系统(CNS)先天性感染的主要病毒病因,可能导致严重的长期后遗症。围产期先天性 HCMV 感染的后遗症发生率高,抗病毒治疗不足,这使得开发 HCMV 特异性疫苗成为现代医学的当务之急。由于 HCMV 的物种特异性,动物模型经常被用于研究 CMV 发病机制。成年小鼠的鼠巨细胞病毒(MCMV)感染研究在 CMV 生物学和发病机制模型方面发挥了重要作用,而新生小鼠的 MCMV 感染已成功用作围产期 CMV 感染的模型。新生感染 MCMV 的小鼠在病毒血症期间具有高病毒载量,在此期间病毒在大多数器官中建立了有活力的感染,同时伴有强烈的炎症反应。在出生后早期,脑组织中的有活力感染导致广泛的非坏死性多灶性脑炎,其特征是固有免疫和适应性免疫的成分浸润。因此,新生小鼠小脑的出生后发育受损导致长期运动和感觉障碍。本章总结了围产期 CMV 感染的啮齿动物模型的最新发现,并描述了分析新生小鼠围产期 MCMV 感染的方法。

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