Abstract

Despite near-annual human outbreaks of Nipah virus (NiV) disease in Bangladesh, typically due to individual spillover events from the local bat population, only twenty whole-genome NiV sequences exist from humans and ten from bats. NiV whole-genome sequences from annual outbreaks have been challenging to generate, primarily due to the low viral load in human throat swab and serum specimens. Here, we used targeted enrichment with custom NiV-specific probes and generated thirty-five additional unique full-length genomic sequences directly from human specimens and viral isolates. We inferred the temporal and geographic evolutionary history of NiV in Bangladesh and expanded a tool to visualize NiV spatio-temporal spread from a Bayesian continuous diffusion analysis. We observed that strains from Bangladesh segregated into two distinct clades that have intermingled geographically in Bangladesh over time and space. As these clades expanded geographically and temporally, we did not observe evidence for significant branch and site-specific selection, except for a single site in the Henipavirus L polymerase. However, the Bangladesh 1 and 2 clades are differentiated by mutations initially occurring in the polymerase, with additional mutations accumulating in the N, G, F, P, and L genes on external branches. Modeling the historic geographical and temporal spread demonstrates that while widespread, NiV does not exhibit significant genetic variation in Bangladesh. Thus, future public health measures should address whether NiV within in the bat population also exhibits comparable genetic variation, if zoonotic transmission results in a genetic bottleneck and if surveillance techniques are detecting only a subset of NiV.

中文翻译：

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尼帕病毒进化推断，1999-2015

摘要

尽管孟加拉国几乎每年都会爆发尼帕病毒（NiV）疾病，通常是由于当地蝙蝠种群的个体溢出事件，但只有 20 个来自人类的全基因组 NiV 序列和 10 个来自蝙蝠的全基因组 NiV 序列。每年爆发的 NiV 全基因组序列很难生成，这主要是由于人类咽拭子和血清样本中的病毒载量较低。在这里，我们使用定制 NiV 特异性探针进行靶向富集，并直接从人类样本和病毒分离株中生成了另外 35 个独特的全长基因组序列。我们推断了孟加拉国 NiV 的时间和地理进化历史，并扩展了一个工具，通过贝叶斯连续扩散分析可视化 NiV 时空传播。我们观察到，来自孟加拉国的菌株分离成两个不同的分支，随着时间和空间的推移，这些分支在孟加拉国地理上混合在一起。随着这些进化枝在地理和时间上的扩展，除了亨尼帕病毒L 聚合酶中的单个位点外，我们没有观察到显着的分支和位点特异性选择的证据。然而，孟加拉国 1 和 2 进化枝是通过聚合酶中最初发生的突变来区分的，另外的突变在外部分支的 N、G、F、P 和 L 基因中积累。对历史地理和时间传播的建模表明，尽管尼病毒广泛存在，但在孟加拉国并未表现出显着的遗传变异。因此，未来的公共卫生措施应解决蝙蝠种群中的 NiV 是否也表现出类似的遗传变异、人畜共患传播是否导致遗传瓶颈以及监测技术是否仅检测到 NiV 的一个子集。