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小鼠模型中高致病性蜱传黄病毒感染的临床评估

Clinical evaluation of highly pathogenic tick-borne flavivirus infection in the mouse model.

作者信息

Tigabu Bersabeh, Juelich Terry, Bertrand Joseph, Holbrook Michael R

机构信息

Department of Pathology and Institute for Human Infections and Immunity, The University of Texas Medical Branch, Galveston, Texas 77555-0609, USA.

出版信息

J Med Virol. 2009 Jul;81(7):1261-9. doi: 10.1002/jmv.21524.

DOI:10.1002/jmv.21524
PMID:19475605
Abstract

The objective of this study was to evaluate the feasibility of using clinical parameters to demonstrate disease progression and differentiate between Omsk hemorrhagic fever virus (OHFV) and Russian spring-summer encephalitis virus (RSSEV) infection in the mouse model. Adult C57BL/6 and balb/c mice were infected with either OHFV or RSSEV by footpad inoculation and their temperature, body weight, clinical signs complete blood count, and blood chemistries were evaluated for up to 15 days post-infection (dpi). Clinical evaluation showed that OHFV infection seriously affects balb/c mice, which had shorter average survival times (ASTs) than other groups. On the contrary, RSSEV infection of C57BL/6 mice was more severe than in balb/c mice. During these studies, the development of fever was not observed and the body weight of OHFV infected balb/c and C57BL/6 mice began to decline sharply starting from day 7 and 8, respectively, which correlated with disease onset. Peak increase of globulin and neutrophils was demonstrated after 9 dpi in OHFV infected mice; however, the lymphocyte number was not affected. Viremia was undetectable in these animals with either virus infection, but virus was found in most organs tested. These results indicate marked differences in the clinical signs, pathology, and immune response of mice infected with either OHFV or RSSEV and further validate the use of this mouse model system to evaluate human disease.

摘要

本研究的目的是评估在小鼠模型中使用临床参数来证明疾病进展以及区分鄂木斯克出血热病毒(OHFV)感染和俄罗斯春夏脑炎病毒(RSSEV)感染的可行性。通过足垫接种将成年C57BL/6和balb/c小鼠感染OHFV或RSSEV,并在感染后长达15天(dpi)评估它们的体温、体重、临床症状、全血细胞计数和血液生化指标。临床评估表明,OHFV感染严重影响balb/c小鼠,其平均存活时间(ASTs)比其他组短。相反,C57BL/6小鼠的RSSEV感染比balb/c小鼠更严重。在这些研究中,未观察到发热现象,感染OHFV的balb/c和C57BL/6小鼠的体重分别从第7天和第8天开始急剧下降,这与疾病发作相关。在感染OHFV的小鼠中,感染后9天球蛋白和中性粒细胞出现峰值升高;然而,淋巴细胞数量未受影响。在这些感染任何一种病毒的动物中均未检测到病毒血症,但在大多数测试器官中发现了病毒。这些结果表明,感染OHFV或RSSEV的小鼠在临床症状、病理学和免疫反应方面存在显著差异,并进一步验证了使用该小鼠模型系统评估人类疾病的可行性。

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