Phylogeography of Lassa virus in Nigeria.

Lassa virus is genetically diverse with several lineages circulating in West Africa. This study aimed at describing the sequence variability of Lassa virus across Nigeria and inferring its spatio-temporal evolution. We sequenced and isolated 77 Lassa virus strains from 16 Nigerian States. The final dataset, including previous works, comprised metadata and sequences of 219 unique strains sampled between 1969 and 2018 in 22 States. Most of this data originated from Lassa fever patients diagnosed at Irrua Specialist Teaching Hospital, Edo State, Nigeria. The majority of sequences clustered with the main Nigerian lineages II and III, while few sequences formed a new cluster related to Lassa virus strains from Within lineages II and III, seven and five sub-lineages, respectively, were distinguishable. The phylogeographic analysis suggests an origin of lineage II in the southeastern part of the country around Ebonyi State and a main vector of dispersal towards the west across the Niger River, through Anambra, Kogi, Delta, and Edo into Ondo State. The frontline of virus dispersal appears to be in Ondo. Minor vectors are directed northeast towards Taraba and Adamawa and south towards Imo and Rivers. Lineage III might have spread from northern Plateau State into Kaduna, Nasarawa, Federal Capital Territory, and Bauchi. One sub-lineage moved south and crossed the Benue River into Benue State. This study provides a geographic mapping of lineages and phylogenetic clusters in Nigeria at higher resolution. In addition, we estimated the direction and timeframe of virus dispersal in the country. Lassa virus is the causative agent of Lassa fever, a viral hemorrhagic fever with a case fatality rate of approximately 30% in Africa. Previous studies disclosed a geographical pattern in the distribution of Lassa virus strains and a westward movement of the virus across West Africa during evolution. Our study provides a deeper understanding of the geography of genetic lineages and sub-lineages of the virus in Nigeria. In addition, we modeled how the virus spread in the country. This knowledge allows predicting into which geographical areas the virus might spread in future and prioritizing areas for Lassa fever surveillance. Our study not only aimed at generating Lassa virus sequences from across Nigeria, but also to isolate and conserve the respective viruses for future research. Both isolates and sequences are important for the development and evaluation of medical countermeasures to treat and prevent Lassa fever, such as diagnostics, therapeutics, and vaccines.