Phylogenetic and evolutionary relationships among yellow fever virus isolates in Africa

Abstract

Previous studies with a limited number of strains have indicated that there are two genotypes of yellow fever (YF) virus in Africa, one in west Africa and the other in east and central Africa. We have examined the prM/M and a portion of the E protein for a panel of 38 wild strains of YF virus from Africa representing different countries and times of isolation. Examination of the strains revealed a more complex genetic relationship than previously reported. Overall, nucleotide substitutions varied from 0 to 25.8% and amino acid substitutions varied from 0 to 9.1%. Phylogenetic analysis using parsimony and neighbor-joining algorithms identified five distinct genotypes: central/east Africa, east Africa, Angola, west Africa I, and west Africa II. Extensive variation within genotypes was observed. Members of west African genotype II and central/east African genotype differed by 2.8% or less, while west Africa genotype I varied up to 6.8% at the nucleotide level. We speculate that the former two genotypes exist in enzootic transmission cycles, while the latter is genetically more heterogeneous due to regular human epidemics. The nucleotide sequence of the Angola genotype diverged from the others by 15.7 to 23.0% but only 0.4 to 5.6% at the amino acid level, suggesting that this genotype most likely diverged from a progenitor YF virus in east/central Africa many years ago, prior to the separation of the other east/central African strains analyzed in this study, and has evolved independently. These data demonstrate that there are multiple genotypes of YF virus in Africa and suggest independent evolution of YF virus in different areas of Africa.

FIG. 1

Neighbor-joining phylogram derived from the nucleotide sequence of the prM/E region of 37 wild YF virus strains from Africa.

FIG. 2

Nucleotide sequence alignment for the distal 108 nucleotides of the premembrane protein gene of 37 YF viruses from tropical Africa. This alignment highlights nucleotide variations among different genotypes and similarities within genotypes. Dots indicate identity with the consensus sequence.

FIG. 3

Amino acid sequence alignment for the prM/E region of 37 YF viruses from Africa. Group-specific amino acid residues are highlighted for each gene. Dots indicate identity with the consensus sequence.

FIG. 3

Amino acid sequence alignment for the prM/E region of 37 YF viruses from Africa. Group-specific amino acid residues are highlighted for each gene. Dots indicate identity with the consensus sequence.

FIG. 4

Amino acid sequence alignment for the structural protein region of four wild-type YF virus strains representing different genotypes.