Ecology of Lassa virus and related arenaviruses in the natural host Mastomys natalensis

拉沙热是一种由拉沙病毒（一种非洲沙粒病毒）引起的人畜共患疾病。该疾病在西非流行，据估计，由于拉沙病毒从啮齿动物宿主（Mastomys natalensis）传播给人类，每年发生10万例感染。采取控制措施，降低病毒在鼠群中的流行率，可降低鼠传人的风险。然而，感染的过程中，病毒-啮齿动物相互作用的动力学，以及啮齿动物种群之间的病毒传播模式知之甚少。因此，本研究项目的一个主要目标是提高对啮齿动物生态学的认识，以便在未来制定适用于流行地区的啮齿动物干预策略。第一阶段计划的主要目标已经部分实现：（1）描述拉沙病毒和相关的莫罗戈罗病毒和莫佩亚病毒的体外和体内基本感染参数;（2）鉴定病毒在自然宿主中持续存在的重要宿主决定因素;（3）确定非洲沙粒病毒在M. natalensis在实验室和现场（坦桑尼亚），使用Morogoro病毒作为可行的模型，和（4）将此信息转化为拉沙病毒传播的数学模型。第二阶段以迄今取得的成果为基础。重点讨论了（1）M. natalensis和新生动物对Morogoro和Mopeia病毒感染的耐受性（2）病毒干扰素拮抗剂与Lassa、Morogoro和Mopeia病毒在体外和体内的生产性复制和持久性的相关性（3）沙粒病毒在野生环境中传播的纵向研究，使用现有和新的数据（4）通过包括脱落和接触率的个体变化来调整初步模型，空间变异和环境随机性和（5）寻找生态因素，以解释在同域和密切相关，但不同的啮齿动物物种的密切相关的沙粒病毒的持久性。由此产生的模型应用于预测丰度阈值和环境条件，低于该阈值，病毒不能在自然宿主种群中持续存在。

Lassa fever is a zoonotic disease caused by Lassa virus, an African arenavirus. The disease is endemic in West Africa and it is estimated that 100,000 infections occur each year as a result of transmission of Lassa virus from its rodent reservoir (Mastomys natalensis) to humans. Control measures aiming at reducing the virus prevalence in the rodent population could reduce the risk of rodent-to-human transmission. However, the course of infection, the dynamics of virus-rodent interaction, and modes of virus transmission among the rodent population are poorly understood. Therefore, a major objective of this research project is to enhance knowledge on rodent ecology to develop, in future, rodent-based intervention strategies that are applicable in the endemic area. Major objectives that were planned for the first stage and have been partially reached were: (1) description of basic infection parameters of Lassa virus and the related Morogoro and Mopeia viruses in vitro and in vivo (2) identification of virus host determinants important for persistence in the natural host (3) determination of modes and timing of transmission of the African arenaviruses among M. natalensis in the laboratory and in the field (Tanzania), using Morogoro virus as a feasible model, and (4) translation of this information into a mathematical model for Lassa virus transmission. The second phase is based on the results obtained so far. It is focused on (1) innate and adaptive immune mechanisms underlying the species barrier in immune cells of M. natalensis and the tolerance of neonatal animals towards infection with Morogoro and Mopeia viruses (2) relevance of the viral interferon antagonist for productive replication and persistence of Lassa, Morogoro, and Mopeia viruses in vitro and in vivo (3) longitudinal studies of arenavirus transmission in the wild, using both existing and new data (4) adjusting the preliminary models by including individual variation in shedding and contact rates, spatial variation and environmental stochasticity and (5) searching for ecological factors to explain the persistence of closely related arenaviruses in sympatric and closely related, but different, rodent species. The resulting model shall be used to predict the abundance threshold and environmental conditions below which the virus cannot persist in the natural host population.