Lethal Infection of Lassa Virus Isolated from a Human Clinical Sample in Outbred Guinea Pigs without Adaptation
Lethal Infection of Lassa Virus Isolated from a Human Clinical Sample in Outbred Guinea Pigs without Adaptation
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DOI：
10.1128/msphere.00428-19
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发表时间：
2019-09-01
期刊：
影响因子：
4.8
通讯作者：
Paessler, Slobodan
中科院分区：
文献类型：
--
作者：
Maruyama, Junki;Manning, John T.;Paessler, Slobodan
拉沙病毒（LASV）是沙粒病毒科的一种病毒，是拉沙热的病原体。拉沙病毒在西非国家流行，如尼日利亚、几内亚、利比里亚和塞拉利昂，每年都会引起疫情。拉沙热开始时有“流感样”症状，严重时可能发展为致命的出血性疾病。虽然从公共卫生的角度来看，拉沙病毒是最令人担忧的病原体之一，但很少有针对拉沙热的许可疫苗或治疗方法。动物模型有限，而且大多数实验室来源的病毒用于研究，这限制了对策的成功开发。在这项研究中，我们证明了LASV分离株LF 2384-NS-DIA-1（LF 2384），它是直接从2012年塞拉利昂爆发的致命性人拉沙热病例的血清样本中分离出来的，在远交哈特利豚鼠中引起一致的致死性感染，而没有病毒宿主适应。这是第一次报告的临床分离株LASV造成致命感染的远交豚鼠。拉沙热的豚鼠模型可能有助于拉沙热的研究和疫苗及治疗药物的开发。重要信息拉沙病毒是拉沙热的病原体，是一种人畜共患病原体，每年在西非国家引起暴发。人类患者在严重的情况下可以发展致命的出血热。虽然从公共卫生的角度来看，拉沙病毒是最令人担忧的病原体之一，但几乎没有可用的对策，如抗病毒药物或疫苗。此外，动物模型不容易获得，而且大多数实验室病毒在分离后已传代多次，用于研究，这进一步限制了对策的成功制定。在这项研究中，我们证明，人类分离的拉沙病毒导致致命的感染一致哈特利豚鼠。这种新的拉沙热动物模型可能有助于拉沙热研究以及疫苗和治疗方法的开发。
Lassa virus (LASV), a member of the family Arenaviridae, is the causative agent of Lassa fever. Lassa virus is endemic in West African countries, such as Nigeria, Guinea, Liberia, and Sierra Leone, and causes outbreaks annually. Lassa fever onset begins with "flu-like" symptoms and may develop into lethal hemorrhagic disease in severe cases. Although Lassa virus is one of the most alarming pathogens from a public health perspective, there are few licensed vaccines or therapeutics against Lassa fever. The fact that animal models are limited and the fact that mostly laboratory-derived viruses are used for studies limit the successful development of countermeasures. In this study, we demonstrated that the LASV isolate LF2384-NS-DIA-1 (LF2384), which was directly isolated from a serum sample from a fatal human Lassa fever case in the 2012 Sierra Leone outbreak, causes uniformly lethal infection in outbred Hartley guinea pigs without virus-host adaptation. This is the first report of a clinically isolated strain of LASV causing lethal infection in outbred guinea pigs. This novel guinea pig model of Lassa fever may contribute to Lassa fever research and the development of vaccines and therapeutics.IMPORTANCE Lassa virus, the causative agent of Lassa fever, is a zoonotic pathogen causing annual outbreaks in West African countries. Human patients can develop lethal hemorrhagic fever in severe cases. Although Lassa virus is one of the most alarming pathogens from a public health perspective, there are few available countermeasures, such as antiviral drugs or vaccines. Moreover, the fact that animal models are not readily accessible and the fact that mostly laboratory viruses, which have been passaged many times after isolation, are used for studies further limits the successful development of countermeasures. In this study, we demonstrate that a human isolate of Lassa virus causes lethal infection uniformly in Hartley guinea pigs. This novel animal model of Lassa fever may contribute to Lassa fever research and the development of vaccines and therapeutics.