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）与淋巴细胞性脉络丛脑膜炎病毒（Lymphocytic choriomeningitis virus, LCMV））可引发人类疾病。多数LCMV与LASV感染由啮齿动物向人类的传播导致。因此，病毒进化在很大程度上由野生宿主库中发生的事件所决定。我们使用一组人类与啮齿动物来源的病毒序列，探究旧世界沙粒病毒物种形成背后的进化历史，以及伴随LASV在西非传播的近期选择事件。研究显示，病毒RNA聚合酶（L protein）是旧世界沙粒病毒以及LASV从尼日利亚向外传播过程中的主要正选择靶点。未观察到糖蛋白（glycoprotein）受到选择的证据，而在LCMV物种形成过程中，正选择作用于核蛋白（NP）。L与NP蛋白中受正选择的位点被高度保守的残基所环绕，病毒基因组的大部分区域在纯化选择（purifying selection）作用下进化。多个受正选择的位点可能调控病毒的复制/转录过程。在L与NP蛋白中，结构特征（溶剂暴露表面积）是决定位点特异性进化速率差异的重要因素。通过纳入多株啮齿动物来源的序列，我们还分析了旧世界沙粒病毒对人类宿主的密码子适配性（codon adaptation）。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（non-Nigerian strains）疾病严重程度”的假说。综上，L与NP蛋白是主要的选择靶点，同时可能是决定疾病表型的关键因素；上述结果提示，野外调查与实验研究应优先聚焦于这两类蛋白。