Differences in Genetic Diversity between Early Isolates of Yellow Fever Virus Genotypes

Yellow fever virus (YFV) is the prototypical member of the genus Orthoflavivirus and is responsible for the disease yellow fever. Phylogenetic studies show YFV can be characterized into seven genotypes (East Africa [EA], East and Central Africa [ECA], West Africa I [WAI], West Africa II [WAII], South America I [SAI], South America II [SAII], and Angola [ANG]). We used Next Generation Sequencing to investigate and compare genetic diversity of the seven genotypes of YFV using early isolated strains of known passage history from a variety of collection years. Genetic diversity varied between the seven genotypes, with the ECA genotype being more diverse than EA and WAI genotypes, but not WAII genotype. Genotype-specific amino acids (GSaas) were identified that occurred in all viral proteins but varied by genotype with most being found in the non-structural proteins, which make up the viral replication complex. Interestingly, the fewest GSaas were found in the EA and ECA genotypes despite the ECA genotype having greater genetic diversity than either the EA or WAI genotypes. Overall, based on examination of early strains, we show that genetic diversity and GSaas varied between the seven genotypes of YFV and are not random but likely caused by selection pressure(s) such as different primate and mosquito hosts in different geographic areas. Examination of genetic diversity and GSaas in recent strains will enable genetic diversity to be investigated over time and those involved in outbreaks may enable a better understanding of how outbreaks develop and help identify interventions to their spread.