Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease
Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease
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DOI：
10.1371/journal.pone.0131742
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发表时间：
2015-07-06
期刊：
影响因子：
3.7
通讯作者：
Hensley, Lisa E.
中科院分区：
文献类型：
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作者：
Mucker, Eric M.;Chapman, Jennifer;Hensley, Lisa E.
虽然目前的猴痘和天花疾病的非人类灵长类动物模型提供了一些关于疾病发病机制的见解，但它们需要高滴度的接种，使用非自然的感染途径，和/或不能准确地代表整个疾病过程。在制定天花和/或猴痘对策或试图了解宿主病原体关系时，这是一个值得关注的问题。在我们的研究中，我们改变了一半的测试系统，使用新世界的非人类灵长类动物宿主，普通狨猴。基于剂量发现研究，我们发现狨猴易受猴痘病毒感染，产生高病毒血症，并具有与人类天花和猴痘一致的病理特征。在使用猴痘病毒的非人灵长类动物模型中，引发统一致命性疾病所需的低剂量（48个斑块形成单位）和较长的潜伏期（临床前症状）是独特的特征。一致的致死率、出疹、高病毒血症、血小板减少、病理和急性期缩短是早期型出血性天花的反映。
Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Based on dose finding studies, we found that marmosets are susceptible to monkeypox virus infection, produce a high viremia, and have pathological features consistent with smallpox and monkeypox in humans. The low dose (48 plaque forming units) required to elicit a uniformly lethal disease and the extended incubation (preclinical signs) are unique features among nonhuman primate models utilizing monkeypox virus. The uniform lethality, hemorrhagic rash, high viremia, decrease in platelets, pathology, and abbreviated acute phase are reflective of early-type hemorrhagic smallpox.