背景:拉沙热是由拉沙病毒(LASV)引起的出血性疾病,世界卫生组织已将其列为需要优先研究的顶级传染病之一。先前的研究为LASV谱系的分类和地理特征提供了见解。然而,该病毒的分布和进化特征以及系统动力学因素仍然有限。
方法:为了增强对LASV的全面了解,我们进行了系统发育分析,重组和重组检测,和变异评估利用公开可用的病毒基因组序列。
结果:结果显示,大(L)段的最新共同祖先(TMRCA)的估计时间根约为634(95%HPD:[385879]),而小(S)段的TMRCA约为1224(95%HPD:[10301401])。LASV主要通过两条路线在西非从东向西传播,在路线2中,病毒通过利比里亚独立传播到周边国家,导致LASV的广泛传播。从1969年到2018年,有效人口规模经历了两次显著增长,表明LASV的遗传多样性增强。我们还发现L段的进化速度比S段快,进一步结果显示锌结合蛋白的进化速度最快。在包括亚谱系IIg在内的多个谱系中检测到重排事件,同时在谱系V内观察到重组事件。鉴定了LASV糖蛋白前体的显着氨基酸变化,证明了LASV谱系之间的序列多样性。
结论:本研究全面阐明了LASV在西非的传播和演变,提供对重组事件的详细见解,重组事件,和氨基酸变异。
BACKGROUND: Lassa fever is a hemorrhagic disease caused by Lassa virus (LASV), which has been classified by the World Health Organization as one of the top infectious diseases requiring prioritized research. Previous studies have provided insights into the classification and geographic characteristics of LASV lineages. However, the factor of the distribution and evolution characteristics and phylodynamics of the virus was still limited.
METHODS: To enhance comprehensive understanding of LASV, we employed phylogenetic analysis, reassortment and recombination detection, and variation evaluation utilizing publicly available viral genome sequences.
RESULTS: The results showed the estimated the root of time of the most recent common ancestor (TMRCA) for large (L) segment was approximately 634 (95% HPD: [385879]), whereas the TMRCA for small (S) segment was around 1224 (95% HPD: [10301401]). LASV primarily spread from east to west in West Africa through two routes, and in route 2, the virus independently spread to surrounding countries through Liberia, resulting in a wider spread of LASV. From 1969 to 2018, the effective population size experienced two significant increased, indicating the enhanced genetic diversity of LASV. We also found the evolution rate of L segment was faster than S segment, further results showed zinc-binding protein had the fastest evolution rate. Reassortment events were detected in multiple lineages including sub-lineage IIg, while recombination events were observed within lineage V. Significant amino acid changes in the glycoprotein precursor of LASV were identified, demonstrating sequence diversity among lineages in LASV.
CONCLUSIONS: This study comprehensively elucidated the transmission and evolution of LASV in West Africa, providing detailed insights into reassortment events, recombination events, and amino acid variations.