Molecular epidemiology of yellow fever virus in Africa: A perspective of the phylogeographic split between East/Central African and West African lineages.

Yellow fever (YF) is a major public-health problem in Africa. Yellow fever virus (YFV), the etiological agent responsible for the disease, exhibits clear delineation of phylogeography between East/Central Africa and West Africa. In order to decipher the genetic nature of the YFV epidemic between these areas, we performed a genome-wide study on its African isolates using the McDonald-Kreitman (MK) test in combination with the type II functional divergence analysis. The results showed that adaptive genetic diversifications have occurred on viral nonstructural protein 1 (NS1) and NS5, which are essential for viral genome replication and immune antagonism, with the East/Central African-West African epidemic split. On both proteins, a number of amino acid replacements have been favored by functional divergence. These findings could help to bridge the gap between the phylogeographic delineation and niche adaptation underlying the YFV-epidemic across Africa and shed light on viral determinants of this process.