Abstract
In this study, we revisited the phylogeography of the three of major DENV-3 genotypes and estimated its rate of evolution, based on the analysis of the envelope (E) gene of 200 strains isolated from 31 different countries around the world over a time period of 50 years (1956–2006). Our phylogenetic analysis revealed a geographical subdivision of DENV-3 population in several country-specific clades. Migration patterns of the main DENV-3 genotypes showed that genotype I was mainly circumspect to the maritime portion of Southeast-Asia and South Pacific, genotype II stayed within continental areas in South-East Asia, while genotype III spread across Asia, East Africa and into the Americas. No evidence for rampant co-circulation of distinct genotypes in a single locality was found, suggesting that some factors, other than geographic proximity, may limit the continual dispersion and reintroduction of new DENV-3 variants. Estimates of the evolutionary rate revealed no significant differences among major DENV-3 genotypes. The mean evolutionary rate of DENV-3 in areas with long-term endemic transmissions ( i.e., Indonesia and Thailand) was similar to that observed in the Americas, which have been experiencing a more recent dengue spread. We estimated the origin of DENV-3 virus around 1890, and the emergence of current diversity of main DENV-3 genotypes between the middle 1960s and the middle 1970s, coinciding with human population growth, urbanization, and massive human movement, and with the description of the first cases of DENV-3 hemorrhagic fever in Asia.
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