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口蹄疫病毒(FMDV)引发的急性疾病可致使成年实验小鼠死亡。

Foot-and-mouth disease virus (FMDV) causes an acute disease that can be lethal for adult laboratory mice.

作者信息

Salguero Francisco J, Sánchez-Martín Miguel A, Díaz-San Segundo Fayna, de Avila Ana, Sevilla Noemí

机构信息

Centro de Investigación en Sanidad Animal, INIA, 28130 Valdeolmos, Madrid, Spain.

出版信息

Virology. 2005 Feb 5;332(1):384-96. doi: 10.1016/j.virol.2004.11.005.

Abstract

Foot-and-mouth disease virus (FMDV) is a picornavirus that causes an acute vesicular disease of cloven-hoofed animals. This virus continues to be threat to livestock worldwide with outbreaks causing severe economic losses. However, very little is known about FMDV pathogenesis, partially due to the inconveniences of working with cattle and swine, the main natural hosts of the virus. Here we demonstrate that C57BL/6 and BALB/C adult mice are highly susceptible to FMDV infection when the virus is administered subcutaneously or intraperitoneally. The first clinical signs are ruffled fur, apathy, humped posture, and wasting, which are followed by neurological signs such as hind-limb paralysis. Within 2-3 days of disease onset, the animals die. Virus is found in all major organs, indicating a systemic infection. Mice developed microvesicles near the basal layer of the epithelium, event that precedes the vesiculation characteristics of FMD. In addition, a lymphoid depletion in spleen and thymus and severe lymphopenia is observed in the infected mice. When these mice were immunized with conventional inactivated FMDV vaccine, they were protected (100% of vaccinated animals) against challenge with a lethal dose of FMDV. The data indicate that this mouse model may facilitate the study of FMDV pathogenesis, and the development of new effective vaccines for FMD.

摘要

口蹄疫病毒(FMDV)是一种小核糖核酸病毒,可引发偶蹄类动物的急性水疱病。这种病毒持续对全球牲畜构成威胁,其爆发会造成严重经济损失。然而,对口蹄疫病毒发病机制的了解却非常有限,部分原因在于该病毒的主要天然宿主牛和猪,在研究中存在诸多不便。在此,我们证明,当通过皮下或腹腔注射方式接种口蹄疫病毒时,C57BL/6和BALB/C成年小鼠对该病毒高度易感。最初的临床症状包括毛发蓬乱、冷漠、驼背姿势和消瘦,随后会出现后肢麻痹等神经症状。在发病后的2至3天内,动物死亡。在所有主要器官中均发现了病毒,表明发生了全身感染。小鼠在上皮细胞基底层附近出现微水疱,这一现象早于口蹄疫典型的水疱形成特征。此外,在受感染小鼠中观察到脾脏和胸腺的淋巴细胞耗竭以及严重的淋巴细胞减少。当用传统的灭活口蹄疫病毒疫苗对这些小鼠进行免疫接种后,它们受到了保护(100%的接种动物),可抵御致死剂量口蹄疫病毒的攻击。这些数据表明,该小鼠模型可能有助于对口蹄疫病毒发病机制的研究,以及开发针对口蹄疫的新型有效疫苗。

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