Adams A Paige, Aronson Judith F, Tardif Suzette D, Patterson Jean L, Brasky Kathleen M, Geiger Robert, de la Garza Melissa, Carrion Ricardo, Weaver Scott C
Department of Pathology and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555, USA.
J Virol. 2008 Sep;82(18):9035-42. doi: 10.1128/JVI.00674-08. Epub 2008 Jul 9.
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.
东部马脑炎病毒（EEEV）在北美（NA）引发最严重的人类虫媒病毒病，并且是一种潜在的生物武器。然而，尽管有感染的血清学证据，但来自南美洲（SA）的基因和抗原性不同的毒株很少与人类疾病或死亡相关。由于小鼠和其他小型啮齿动物对北美病毒和南美病毒的反应与人类不同，我们通过鼻内感染并监测体重减轻、发热、厌食、抑郁和神经症状，对普通狨猴（Callithrix jacchus）进行了测试。感染北美EEEV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，但感染南美EEEV的动物保持健康并存活下来。感染南美EEEV的动物在感染后第2天或第4天出现病毒血症峰值，滴度为2.8至3.1 log(10) PFU/ml，但感染北美EEEV的动物未检测到病毒血症。相比之下，在安乐死或死亡时，在感染北美EEEV的动物的脑、肝和肌肉中检测到了病毒。与人类EEE所描述的脑损伤相似，感染北美EEEV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。这项研究的结果确定普通狨猴是用于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一些（如果不是全部）南美EEEV毒株对人类减毒的流行病学证据方面的潜力。
