DVM, Major, US Army, US Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, USA.
Vet Pathol. 2010 Sep;47(5):852-70. doi: 10.1177/0300985810378649. Epub 2010 Aug 3.
Smallpox was one of the most devastating diseases known to humanity. Although smallpox was eradicated through a historically successful vaccination campaign, there is concern in the global community that either Variola virus (VARV), the causative agent of smallpox, or another species of Orthopoxvirus could be used as agents of bioterrorism. Therefore, development of countermeasures to Orthopoxvirus infection is a crucial focus in biodefense research, and these efforts rely on the use of various animal models. Smallpox typically presented as a generalized pustular rash with 30 to 40% mortality, and although smallpox-like syndromes can be induced in cynomolgus macaques with VARV, research with this virus is highly restricted; therefore, animal models with other orthopoxviruses have been investigated. Monkeypox virus causes a generalized vesiculopustular rash in rhesus and cynomolgus macaques and induces fatal systemic disease in several rodent species. Ectromelia virus has been extensively studied in mice as a model of orthopoxviral infection in its natural host. Intranasal inoculation of mice with some strains of vaccinia virus produces fatal bronchopneumonia, as does aerosol or intranasal inoculation of mice with cowpox virus. Rabbitpox virus causes pneumonia and fatal systemic infections in rabbits and can be naturally transmitted between rabbits by an aerosol route similar to that of VARV in humans. No single animal model recapitulates all known aspects of human Orthopoxvirus infections, and each model has its advantages and disadvantages. This article provides a brief review of the Orthopoxvirus diseases of humans and the key pathologic features of animal models of Orthopoxvirus infections.
天花是人类已知的最具破坏性的疾病之一。尽管通过历史上成功的疫苗接种运动根除了天花，但全球社会仍担心天花病毒（VARV）或另一种正痘病毒可能被用作生物恐怖主义的手段。因此，开发针对正痘病毒感染的对策是生物防御研究的关键重点，这些努力依赖于使用各种动物模型。天花通常表现为全身性脓疱疹，死亡率为 30%至 40%，尽管可以用 VARV 在食蟹猴中诱导出类似天花的综合征，但对这种病毒的研究受到高度限制；因此，已经研究了其他正痘病毒的动物模型。猴痘病毒在恒河猴和食蟹猴中引起全身性水疱脓疱疹，并在几种啮齿动物中引起致命的全身性疾病。在其自然宿主中，作为正痘病毒感染模型，兔痘病毒在小鼠中已得到广泛研究。某些毒株的牛痘病毒鼻内接种可导致小鼠致命性支气管肺炎，气溶胶或鼻内接种可导致小鼠致命性全身感染。兔痘病毒在兔中引起肺炎和致命的全身感染，并且可以通过类似于人类 VARV 的气溶胶途径在兔之间自然传播。没有单一的动物模型可以重现人类正痘病毒感染的所有已知方面，每种模型都有其优点和缺点。本文简要回顾了人类正痘病毒病和正痘病毒感染动物模型的关键病理特征。
