GEOGRAPHIC-DISTRIBUTION AND EVOLUTION OF YELLOW-FEVER VIRUSES BASED ON DIRECT SEQUENCING OF GENOMIC CDNA FRAGMENTS

We have compared the nucleotide sequence of an envelope protein gene f ragment encoding amino acids 291 to 406 of 22 yellow fever (YF) virus strains of diverse geographic and host origins isolated over a 63 year time span. The nucleotide fragment of viral RNA was examined by direc t sequencing of a PCR product derived from complementary DNA. Alignmen t with the prototype Asibi strain sequence showed divergence of 0 to 2 1.5% corresponding to a maximum of 5.2% divergence in the amino acid s equence. Taking 10% nucleotide divergence as a cut-off point, the 22 Y F virus strains fell into three topotypes which corresponded to differ ent geographical areas, namely West Africa, Central-East Africa, and S outh America, Two subgroups were defined in West Africa, a genotypic g roup circulating in the sylvatic zone of the western part of Africa, f rom western Ivory Coast-Mall to Senegal, and a group responsible for l arge outbreaks from eastern Ivory Coast-Burkina Faso to Cameroon. Stra ins from Central-East Africa showed a low ratio of transition: transve rsion of about 1 instead of 8 to 10 for other strains, when their nucl eotide sequences were compared with those of other African strains. Th is may reflect a more distant relationship between the former strains and the others. No change was observed in the highly conserved amino a cid domain encompassing the TGD sequence, an important determinant of flavivirus tropism and pathogenesis. Our results support earlier obser vations on the genetic relationships between YF isolates established b y T1 oligonucleotide fingerprinting and offer a useful tool for the un derstanding of YF virus distribution and evolution.