Adaptive Diversification between Yellow Fever Virus West African and South American Lineages: A Genome-Wide Study

摘要

Yellow fever virus (YFV) has emerged as the causative agent of a vector-borne disease with devastating mortality in the tropics of Africa and the Americas. YFV phytogenies indicate that the isolates collected from West Africa, East and Central Africa, and South America cluster into different lineages and the virus spread into the Americas from Africa. To determine the nature of genetic variation accompanying the intercontinental epidemic, we performed a genome-wide evolutionary study on the West African and South American lineages of YFV. Our results reveal that adaptive genetic diversification has occurred on viral nonstructural protein 5 (NS5), which is crucially required for viral genome replication, in the early epidemic phase of these currently circulating lineages. Furthermore, major amino acid changes relevant to the adaptive diversification generally cluster in different structural regions of NS5 in a lineage-specific manner. These results suggest that YFV has experienced adaptive diversification in the epidemic spread between the continents and shed insights into the genetic determinants of such diversification, which might be beneficial for understanding the emergence and re-emergence of yellow fever as an important global public health issue. Yellow fever (YF) is an acute hemorrhagic disease caused by arthropod-transmitted yellow fever virus (YFV). The large scale outbreaks of YF in Africa, North and South America, and Europe resulted in devastating mortality from the fifteenth to nineteenth centuries. YF currently remains an important global public health concern. For example, the burden of YF was 84,000-170,000 severe cases and 29,000-60,000 deaths in tropical areas of Africa and South America during 2013. YFV possesses a single-stranded, positive-sense RNA genome. The genome consists of two untranslated regions at the 5'- and 3'- ends, and an open reading frame. The open reading frame is translated as a single polyprotein, which is further cleaved into 10 mature proteins by host cellular signal peptidase and virally encoded proteases.