Common marmosets (Callithrix jacchus) as a nonhuman primate model to assess the virulence of eastern equine encephalitis virus strains
Common marmosets (Callithrix jacchus) as a nonhuman primate model to assess the virulence of eastern equine encephalitis virus strains
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DOI：
10.1128/jvi.00674-08
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发表时间：
2008-09-01
影响因子：
5.4
通讯作者：
Weaver, Scott C.
中科院分区：
文献类型：
--
作者：
Adams, A. Paige;Aronson, Judith F.;Weaver, Scott C.
东部马脑炎病毒（EEEV）是北美地区最严重的人类虫媒病毒性疾病，是一种潜在的生物武器。然而，来自南美的遗传和抗原性不同的菌株很少与人类疾病或死亡有关，尽管有血清学证据表明感染。由于小鼠和其他小型啮齿动物对NA和SA病毒的反应与人类不同，我们通过鼻内感染和监测体重减轻、发烧、厌食症、抑郁和神经症状来测试普通狨猴（Callithrix jacchus）。NA型eeev感染的动物在感染后第4天或第5天因厌食和神经症状死亡或被安乐死，而SA型eeev感染的动物保持健康并存活。SA型eeev感染动物在感染后第2天或第4天出现2.8 ~ 3.1 log(10) PFU/ml的病毒滴度峰值，而NA型eeev感染动物未检测到病毒滴度。相比之下，在安乐死或死亡时，NA eeev感染动物的大脑，肝脏和肌肉中检测到病毒。与人类EEE的脑损伤类似，NA eeev感染的动物在大脑皮层出现脑膜脑炎，并伴有一些血管周围出血。本研究的发现确定了普通狨猴作为测试抗病毒药物和候选疫苗的人类EEE的有用模型，并强调了它们在证实流行病学证据方面的潜力，即一些（如果不是全部的话）SA EEEV毒株对人类是减毒的。
Eastern equine encephalitis virus ( EEEV) produces the most severe human arboviral disease in North America (NA) and is a potential biological weapon. However, genetically and antigenically distinct strains from South America (SA) have seldom been associated with human disease or mortality despite serological evidence of infection. Because mice and other small rodents do not respond differently to the NA versus SA viruses like humans, we tested common marmosets (Callithrix jacchus) by using intranasal infection and monitoring for weight loss, fever, anorexia, depression, and neurologic signs. The NA EEEV-infected animals either died or were euthanized on day 4 or 5 after infection due to anorexia and neurologic signs, but the SA EEEV-infected animals remained healthy and survived. The SA EEEV-infected animals developed peak viremia titers of 2.8 to 3.1 log(10) PFU/ml on day 2 or 4 after infection, but there was no detectable viremia in the NA EEEV-infected animals. In contrast, virus was detected in the brain, liver, and muscle of the NA EEEV-infected animals at the time of euthanasia or death. Similar to the brain lesions described for human EEE, the NA EEEV-infected animals developed meningoencephalitis in the cerebral cortex with some perivascular hemorrhages. The findings of this study identify the common marmoset as a useful model of human EEE for testing antiviral drugs and vaccine candidates and highlight their potential for corroborating epidemiological evidence that some, if not all, SA EEEV strains are attenuated for humans.