Natural History of Aerosol Induced Lassa Fever in Non-Human Primates
Natural History of Aerosol Induced Lassa Fever in Non-Human Primates
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DOI：
10.3390/v12060593
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发表时间：
2020-06-01
期刊：
影响因子：
4.7
通讯作者：
Honko, Anna
中科院分区：
文献类型：
--
作者：
Downs, Isaac L.;Shaia, Carl, I;Honko, Anna
拉沙病毒（LASV）是一种引起拉沙热的沙粒病毒，在西非流行，每年有多达30万例病例和5000至10,000例死亡。拉沙病毒在美国很少见，是CDC A类生物制剂，因为与自然获得的感染相比，故意的气溶胶暴露可能具有高死亡率。由于需要动物模型，由于没有FDA批准的疫苗，具体的对策仍然难以捉摸。在连续遥测监测下研究了食蟹猴暴露于气溶胶化拉沙病毒的自然史。猕猴对激发的反应在很大程度上类似于严重的人类疾病，包括发热、心动过速、低血压和呼吸急促。在初始观察期间，病毒糖蛋白阳性的活化单核细胞呈增加趋势，伴有淋巴细胞减少。疾病一致进展为高病毒血症，随后为低阴离子间隙、水肿、贫血和血小板减少。感染后期出现低蛋白血症，随后出现白色血细胞、细胞因子、趋化因子和肝损伤生化标志物水平升高。在终点时，在三名非幸存者的组织中检测到病毒核酸，但在唯一的幸存者中未检测到病毒核酸。这项研究提供了有用的细节，基准的关键模型拉沙热，以支持地方病和传统的生物防御目的的医疗对策发展。
Lassa virus (LASV), an arenavirus causing Lassa fever, is endemic to West Africa with up to 300,000 cases and between 5000 and 10,000 deaths per year. Rarely seen in the United States, Lassa virus is a CDC category A biological agent inasmuch deliberate aerosol exposure can have high mortality rates compared to naturally acquired infection. With the need for an animal model, specific countermeasures remain elusive as there is no FDA-approved vaccine. This natural history of aerosolized Lassa virus exposure inMacaca fasciculariswas studied under continuous telemetric surveillance. The macaque response to challenge was largely analogous to severe human disease with fever, tachycardia, hypotension, and tachypnea. During initial observations, an increase trend of activated monocytes positive for viral glycoprotein was accompanied by lymphocytopenia. Disease uniformly progressed to high viremia followed by low anion gap, alkalosis, anemia, and thrombocytopenia. Hypoproteinemia occurred late in infection followed by increased levels of white blood cells, cytokines, chemokines, and biochemical markers of liver injury. Viral nucleic acids were detected in tissues of three non-survivors at endpoint, but not in the lone survivor. This study provides useful details to benchmark a pivotal model of Lassa fever in support of medical countermeasure development for both endemic disease and traditional biodefense purposes.