Genetic variation and microevolution of dengue 2 virus in Southeast Asia

Dengue 2 (DEN 2) virus strains collected from dengue hemorrhagic fever (DHF) patients and Aedes aegypti mosquitoes in Thailand, Burma, and Vietnam over a 25-year period have been analyzed by computer assisted Ti-RNase-resistant oligonucleotide fingerprinting. Fifty-seven DEN 2 virus strains of the Thailand topotype were separated into four major clusters by phylogenetic analysis of 97 unique oligonucleotides identified in a common well-resolved region of the fingerprints. Similarities in the 57 fingerprints indicated that DEN 2 virus of a single, continually evolving genetic population has been involved in endemic transmission of the disease. Virus isolates from DHF cases and mosquitoes are genetically very similar, indicating that different genetic topotypes are not selectively the cause of severe DEN disease in Thailand. Microevolution of the DEN 2 virus genome from 1962-1986 was gradual with detectable changes in the pattern of oligonucleotides through time. Segregation of the DEN 2 virus fingerprints into the three decades (1960s, 1970s, and 1980s) revealed the rate of genetic change to be one consensus oligonucleotide per year. Based on average association coefficient (S_ab) values between the consensus fingerprints for each decade, the similarity between the consensus fingerprints decreased by 1.4% per year. Genetic variation during each of the three decades was found to be essentially the same (0.866 ± 0.053). Constancy in the microevolutionary rate and genetic variability suggests that a balance of genetic drift and natural selection acting on the viral population did not significantly change throughout the 25-year period.