Circulation of Lassa virus across the endemic Edo-Ondo axis, Nigeria, with cross-species transmission between multimammate mice

We phylogenetically compared sequences of the zoonotic Lassa virus (LASV) obtained from Mastomys rodents in seven localities across the highly endemic Edo and Ondo States within Nigeria. Sequencing 1641 nt from the S segment of the virus genome, we resolved clades within lineage II that were either limited to Ebudin and Okhuesan in Edo state (2g-beta) or along Owo-Okeluse-Ifon in Ondo state (2g-gamma). We also found clades within Ekpoma, a relatively large cosmopolitan town in Edo state, that extended into other localities within Edo (2g-alpha) and Ondo (2g-delta). LASV variants from M. natalensis within Ebudin and Ekpoma in Edo State (dated approximately 1961) were more ancient compared to those from Ondo state (approximately 1977), suggesting a broadly east-west virus migration across south-western Nigeria; a pattern not always consistent with LASV sequences derived from humans in the same localities. Additionally, in Ebudin and Ekpoma, LASV sequences between M. natalensis and M. erythroleucus were interspersed on the phylogenetic tree, but those from M. erythroleucus were estimated to emerge more recently (approximately 2005). Overall, our results show that LASV amplification in certain localities (reaching a prevalence as high as 76% in Okeluse), anthropogenically-aided spread of rodent-borne variants amidst the larger towns (involving communal accommodation such as student hostels), and virus-exchange between syntopic M. natalensis and M. erythroleucus rodents (as the latter, a savanna species, encroaches southward into the degraded forest) pose perpetual zoonotic hazard across the Edo-Ondo Lassa fever belt, threatening to accelerate the dissemination of the virus into non endemic areas.本研究针对尼日利亚拉沙热高流行区埃多州与翁多州境内7个采样点的多乳鼠属（Mastomys）啮齿动物分离获得的拉沙病毒（Lassa virus, LASV）序列开展系统发育比较分析。我们对该病毒基因组S片段的1641个核苷酸（nucleotide, nt）进行测序，解析出世系II内的两类进化支：一类仅分布于埃多州埃布丁（Ebudin）与奥库桑（Okhuesan），命名为2g-β型；另一类分布于翁多州奥沃-奥克鲁瑟-伊丰（Owo-Okeluse-Ifon）沿线，命名为2g-γ型。此外，我们在埃多州规模较大的城镇埃克波马（Ekpoma）内发现了另一类进化支，该进化支可扩散至埃多州境内其他采样点（2g-α型）及翁多州境内采样点（2g-δ型）。埃多州埃布丁与埃克波马地区纳塔尔多乳鼠（Mastomys natalensis）携带的LASV变异株进化年代约为1961年，较翁多州来源的变异株（约1977年）更为久远，这提示拉沙病毒在尼日利亚西南部存在大范围东西向迁移；但该模式与同采样点人类来源的LASV序列并不完全契合。此外，在埃布丁与埃克波马地区，纳塔尔多乳鼠与红颊多乳鼠（Mastomys erythroleucus）来源的LASV序列在系统发育树上呈穿插分布，但红颊多乳鼠来源的序列估计出现时间更晚（约2005年）。综上，本研究结果表明：部分采样点内的LASV扩增现象（奥克鲁瑟地区感染率最高可达76%）、大型城镇中啮齿动物携带的变异株借助人为活动扩散（涉及学生宿舍等集体住宿场景），以及同域分布的纳塔尔多乳鼠与红颊多乳鼠间的病毒交换（红颊多乳鼠作为稀树草原物种，正向南入侵退化森林地带），共同在埃多-翁多州拉沙热流行带构成了持续存在的人畜共患风险，并有加速病毒向非流行区扩散的威胁。