Genetic basis underlying Lassa fever endemics in the Mano River region, West Africa

Lassa fever (LF), a haemorrhagic fever disease caused by Lassa virus (LASV), is a serious public health burden in West Africa. The Mano River region (Sierra Leone, Guinea, Liberia, and Côte d'Ivoire) has been an endemic focus of the disease over the past decades. Here, we deciphered the genetic basis underlying LF endemics in this region. Clade model and type I functional divergence analyses revealed that the major LASV group, Kenema sub-clade, which is currently circulating in the Eastern Province of Sierra Leone, has been affected by different selective pressure compared to isolates from the other areas with effects on the viral RNA-dependent RNA polymerase (L protein) and probably nucleoprotein (NP). Further, contingency analysis showed that, in the early endemic, the sub-clade has undergone adaptive diversification via acceleration of amino acid substitutions in L protein. These findings highlight the key viral factor and local adaptation regarding the endemicity of LF.