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以小鼠的细小病毒感染为模型支持抗正痘病毒治疗药物的许可。

Ectromelia virus infections of mice as a model to support the licensure of anti-orthopoxvirus therapeutics.

机构信息

Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1100 S. Grand Blvd., St. Louis, MO, 63104, USA.

Chimerix Inc., 2505 Meridian Park Way, Suite 340, Durham, NC, 27713, USA.

出版信息

Viruses. 2010 Sep;2(9):1918-1932. doi: 10.3390/v2091918. Epub 2010 Sep 3.

DOI:10.3390/v2091918
PMID:21994714
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3185751/
Abstract

The absence of herd immunity to orthopoxviruses and the concern that variola or monkeypox viruses could be used for bioterroristic activities has stimulated the development of therapeutics and safer prophylactics. One major limitation in this process is the lack of accessible human orthopoxvirus infections for clinical efficacy trials; however, drug licensure can be based on orthopoxvirus animal challenge models as described in the "Animal Efficacy Rule". One such challenge model uses ectromelia virus, an orthopoxvirus, whose natural host is the mouse and is the etiological agent of mousepox. The genetic similarity of ectromelia virus to variola and monkeypox viruses, the common features of the resulting disease, and the convenience of the mouse as a laboratory animal underscores its utility in the study of orthopoxvirus pathogenesis and in the development of therapeutics and prophylactics. In this review we outline how mousepox has been used as a model for smallpox. We also discuss mousepox in the context of mouse strain, route of infection, infectious dose, disease progression, and recovery from infection.

摘要

由于对正痘病毒缺乏群体免疫力,并且担心天花或猴痘病毒可能被用于生物恐怖主义活动,这刺激了治疗方法和更安全的预防措施的发展。在这个过程中,一个主要的限制是缺乏可用于临床疗效试验的可及的人类正痘病毒感染;然而,药物许可可以基于正痘病毒动物挑战模型,如“动物疗效规则”中所述。这样的一个挑战模型使用的是细弱病毒,一种正痘病毒,其自然宿主是小鼠,是小鼠痘的病原体。细弱病毒与天花和猴痘病毒的遗传相似性、由此产生的疾病的共同特征,以及小鼠作为实验室动物的便利性,突出了它在正痘病毒发病机制研究以及治疗方法和预防措施开发中的效用。在这篇综述中,我们概述了如何将小鼠痘作为天花模型。我们还讨论了小鼠痘在小鼠品系、感染途径、感染剂量、疾病进展和从感染中恢复等方面的情况。

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Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):838-43. doi: 10.1073/pnas.0912134107. Epub 2009 Dec 22.
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