Data from: Evolutionary analysis of Old World arenaviruses reveals a major adaptive contribution of the viral polymerase

The Old World (OW) arenavirus complex includes several species of rodent-borne viruses, some of which (i.e., Lassa virus, LASV and Lymphocytic choriomeningitis virus, LCMV) cause human diseases. Most LCMV and LASV infections are caused by rodent-to-human transmissions. Thus, viral evolution is largely determined by events that occur in the wildlife reservoirs. We used a set of human- and rodent-derived viral sequences to investigate the evolutionary history underlying OW arenavirus speciation, as well as the more recent selective events that accompanied LASV spread in West Africa. We show that the viral RNA polymerase (L protein) was a major positive selection target in OW arenaviruses and during LASV out-of-Nigeria migration. No evidence of selection was observed for the glycoprotein, whereas positive selection acted on the nucleoprotein (NP) during LCMV speciation. Positively selected sites in L and NP are surrounded by highly conserved residues, and the bulk of the viral genome evolves under purifying selection. Several positively selected sites are likely to modulate viral replication/transcription. In both L and NP, structural features (solvent exposed surface area) are important determinants of site-wise evolutionary rate variation. By incorporating several rodent-derived sequences, we also performed an analysis of OW arenavirus codon adaptation to the human host. Results do not support a previously hypothesized role of codon adaptation in disease severity for non-Nigerian strains. In conclusion, L and NP represent the major selection targets and possible determinants of disease presentation; these results suggest that field surveys and experimental studies should primarily focus on these proteins.旧世界（Old World, OW）沙粒病毒复合体包含多种啮齿动物传播的病毒，其中部分病毒（即拉沙病毒（Lassa virus, LASV）与淋巴细胞脉络丛脑膜炎病毒（Lymphocytic choriomeningitis virus, LCMV））可引发人类疾病。多数淋巴细胞脉络丛脑膜炎病毒及拉沙病毒感染均由啮齿动物向人类传播。因此，病毒的演化在很大程度上由其野生动物宿主库中的事件所决定。本研究利用一组源自人类与啮齿动物的病毒序列，探究旧世界沙粒病毒物种形成背后的演化历史，以及伴随拉沙病毒在西非传播的近期选择事件。研究发现，病毒RNA依赖RNA聚合酶（viral RNA-dependent RNA polymerase, L蛋白）是旧世界沙粒病毒以及拉沙病毒走出尼日利亚传播阶段的主要正选择靶点。糖蛋白（glycoprotein）未检测到选择信号，而在淋巴细胞脉络丛脑膜炎病毒的物种形成过程中，核蛋白（nucleoprotein, NP）受到正选择作用。L蛋白与核蛋白中的正选择位点周围存在高度保守的氨基酸残基，病毒基因组的绝大部分区域均处于纯化选择（purifying selection）压力下演化。多个正选择位点可能参与调控病毒的复制与转录过程。在L蛋白与核蛋白中，结构特征（即溶剂暴露表面积）是决定位点特异性演化速率差异的重要因素。本研究还纳入多组啮齿动物来源的病毒序列，分析了旧世界沙粒病毒对人类宿主的密码子适配性。研究结果不支持此前提出的“密码子适配性影响非尼日利亚毒株疾病严重程度”的假说。综上，L蛋白与核蛋白是主要的选择靶点，同时可能是疾病表现型的关键决定因素；本研究结果提示，野外调查与实验研究应优先聚焦于这两类蛋白。