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

自然宿主 Mastomys natalensis 中拉沙病毒和相关沙粒病毒的生态学

• 批准号: 226377141
• 负责人: Professor Dr. Stephan Günther
• 金额: --
• 依托单位: Evolutionary Ecology Group
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/226377141?language=en
• 关键词: Ecology; Lassa; virus; related; arenaviruses

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.

拉沙热是一种由非洲阿拉伯病毒拉萨病毒引起的人畜共患病。这种疾病在西非流行，据估计，每年有10万人感染拉萨病毒，原因是拉萨病毒从其啮齿动物宿主(Mastomys Natalensis)传播给人类。旨在降低啮齿动物种群中病毒流行率的控制措施可以降低啮齿动物传人的风险。然而，对感染过程、病毒与啮齿动物相互作用的动态以及病毒在啮齿动物群体中的传播方式还知之甚少。因此，这项研究项目的一个主要目标是加强对啮齿动物生态学的了解，以便在未来制定适用于流行区的以啮齿动物为基础的干预策略。第一阶段计划并已部分实现的主要目标是：(1)描述拉萨病毒及相关的莫罗戈罗病毒和莫佩亚病毒在体外和体内的基本感染参数；(2)确定对在自然宿主中持续存在重要的病毒宿主决定因素；(3)在实验室和现场(坦桑尼亚)，使用莫罗戈罗病毒作为可行的模型，确定非洲虫媒病毒在纳塔尔分枝杆菌中的传播方式和传播时间，以及(4)将这些信息转化为拉萨病毒传播的数学模型。第二阶段是以迄今取得的成果为基础。主要集中在(1)纳塔尔分枝杆菌免疫细胞中物种屏障的先天和适应性免疫机制以及新生动物对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有效复制和持久性的相关性(3)利用现有数据和新数据对ArenaVirus在野外传播的纵向研究(4)通过包括脱落和接触率的个体差异、空间差异和环境随机性来调整初步模型，以及(5)寻找生态因素来解释密切相关的Arenaia病毒在共生和密切相关但不同的啮齿动物物种中的持久性。由此产生的模型应用于预测病毒在自然宿主种群中不能持续存在的丰度阈值和环境条件。