Molecular epidemiology of dengue viruses from complete genome sequences

The availability of the complete genetic blueprint of the dengue virus is essential in molecular epidemiological studies to uncover the role of the virus in dengue pathogenesis. During the course of this project, over two hundred complete genomes of the dengue virus were generated from clinical samples collected in three dengue-endemic Southeast Asian countries. In addition, a bioinformatics platform integrating a sequence database, sequence retrieval tools, sequence annotation data and a variety of analysis tools was developed for easy management, manipulation and analysis of dengue virus sequence data. Whereas previous studies have mostly focused on epidemiological events in the Americas and Thailand, sequence data recovered from dengue epidemics in Indonesia, Malaysia and Singapore in this study have uncovered some of the dengue virus diversity circulating in the region. The three countries appear to share similar pool of dengue viruses, with some viral lineages in sustained circulation since at least the 1970s. Sequencing of historical virus isolates prior to the 2004/2005 epidemics in Indonesia and Singapore revealed that adaptive viral evolution played little or no role in triggering those epidemics. Lastly, a method that utilised all available sequence data from Malaysia was devised to reconstruct the history of dengue virus in that country since the 1960s.