Study of Nipah virus dynamics and genetics in its bat reservoir and of human exposure to NiV across Bangladesh to understand patterns of human outbreaks

项目摘要 尼帕病毒是一种人畜共患的副粘病毒，由东半球的果蝠携带，横跨非洲和亚洲，引起 严重的、致命的人类脑炎，可在人与人之间传播。在孟加拉国，那里 每年在人中暴发，主要传播途径是食用生棕榈汁。 枣树汁液在孟加拉国西部收获和消费最密集，该地区被称为 然而，“尼帕带”存在着椰枣汁液的消费，以及它的蝙蝠储藏库--中翼翼手。 在整个孟加拉。目前尚不清楚为什么孟加拉国东部没有检测到疫情。神秘莫测 新城疫病毒的溢出产生了一个重大风险，即更多的致病和可传播的毒株将出现并导致 到大规模的流行病。这一多学科项目将确定新城疫疫情是否在#年发生。 孟加拉东部以及人类行为、蝙蝠感染模式和 新城疫病毒的循环毒株影响尼帕带以外的疫情。这个项目结合了人类的暴露 蝙蝠多部位纵向感染研究和蝙蝠体内实验感染研究 仓鼠比较不同菌株之间的临床结果，以实现以下特定目标： 1)比较室内和室外人群中新城疫病毒暴露及其行为决定因素 在孟加拉的尼帕带外。我们将检验NIV溢出已经发生在 在尼帕带以外的社区中的孟加拉国。我们将使用行为问卷和多个 Luminex血清学试验筛查高危人群新城疫抗体并确定 已经发生的Nipah暴露以及行为风险如何因地区而异。 2)比较Nipah病毒在翼蝙蝠种群内外的时间动态 尼帕腰带。我们将在六个地点(西部三个，东部三个)进行纵向BAT Niv实地研究， 描述当地蝙蝠的人口学特征，测量血清阳性率随时间的变化；确定病毒 菌株间的脱落模式和遗传变异。通过在BSL 4中实验感染蝙蝠 实验室，我们将确定携带抗新城疫病毒抗体的蝙蝠是否会再次感染 并释放病毒。这将回答一个关于变速器动力学的关键问题，并使我们能够测试 假设病毒在东部蝙蝠和西部蝙蝠中发生的频率不同， 这可能会影响人畜共患传播。 3)比较蝙蝠体内不同尼帕病毒分离株的致病性和传播性。 在尼帕带外，使用动物模型。马来西亚型Niv和孟加拉型不同 人类的临床特征。新城疫病毒基因变异可能是东部地区人类感染率较低的原因 孟加拉。为了验证这一假设，我们将比较不同新城疫病毒的传播性和致病性。 在BSL 4条件下从叙利亚仓鼠模型中分离到的中间翼毛虫菌株。

Project Summary Nipah virus is a zoonotic paramyxovirus, carried by old world fruit bats across Africa and Asia, which causes severe, fatal encephalitis in humans and can be transmitted from person to person. In Bangladesh, where outbreaks in people occur annually, the primary route of transmission is the consumption of raw date palm sap. Date palm sap is harvested and consumed most intensively in western Bangladesh, an area referred to as the “Nipah belt,” however, date palm sap consumption, NiV, and its bat reservoir, Pteropus medius, are present throughout Bangladesh. It is unclear why outbreaks have not been detected in eastern Bangladesh. Cryptic spillover of NiV creates a significant risk that more pathogenic and transmissible strains will emerge and lead to large epidemics. This multidisciplinary project will determine whether NiV outbreaks have occurred in eastern Bangladesh and how differences human behavior, infection patterns in bats, and genetic variation in circulating strains of NiV influence outbreaks outside of the Nipah belt. This project combines human exposure studies with multi-site longitudinal infection studies in bats and in vivo experimental infections in bats and hamsters comparing clinical outcomes among diverse strains to achieve the following specific aims: 1) To compare NiV exposure and its behavioral determinants among human populations inside and outside the Nipah belt in Bangladesh. We will test the hypothesis that NiV spillover has occurred in Bangladesh in communities outside the Nipah belt. We’ll use behavioral questionnaires and a multiplex Luminex serological assay to screen high risk populations for IgG antibodies against NiV and determine if Nipah exposure has occurred and how behavioral risk varies by locality. 2) To compare Nipah virus temporal dynamics in Pteropus bat colonies inside and outside of the Nipah belt. We will conduct longitudinal bat NiV field studies in six locations (3 western, 3 eastern), characterize local bat demography, measure changes in seroprevalence over time; determine viral shedding patterns and genetic variation among strains. Through experimental bat infections in a BSL 4 lab, we will determine whether bats with antibodies against NiV (previous exposure) may be re-infected and shed virus. This will answer a critical question about transmission dynamics and allow us to test the hypothesis that viral shedding occurs with different frequency in eastern bats compared to western bats, which may influence zoonotic transmission. 3) To compare pathogenicity and transmissibility of diverse Nipah virus isolates from bats inside and outside the Nipah belt, using animal models. Malaysia type NiV and Bangladesh type have different clinical profiles in people. NiV genetic variation may account for lower human infection rates in eastern Bangladesh. To test this hypothesis, we will compare transmissibility and pathogenicity of diverse NiV strains isolated from Pteropus medius in a Syrian hamster model under BSL 4 conditions.