RNA oligonucleotide fingerprinting studies on a large number of virus isolates previously demonstrated considerable genetic variation in isolates of dengue (DEN-)-2 serotype. We report the entire envelope (E) glycoprotein gene and deduced amino acid sequences of 16 DEN-2 viruses and the phylogenetic relationships of these, plus 17 additional published DEN E gene sequences. Comparison of DEN-2 E glycoprotein gene sequences revealed base substitutions scattered throughout the entire gene with as much as 22% sequence divergence. Aligned E glycoprotein amino acid sequences revealed the viruses differed by as much as 10%. There appeared to be constraints on the overall structure of the E protein to maintain biological function. Clusters of amino acid substitutions were present in the hydrophobic membrane anchor region at the carboxyl terminal end of the protein. Maximum parsimony analysis of the E gene sequences allowed construction of a phylogram indicating evolutionary relationships of the virus isolates within the DEN-2 serotype. Five genetic subtypes were identified. Phylogenetic relationships of the DEN-2 serotype and other flaviviruses based on E protein sequences reflected traditional antigenic and serologic classifications.
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