Natural attenuation of dengue virus type-2 after a series of island outbreaks: a retrospective phylogenetic study of events in the South Pacific three decades ago.

Dengue is an expanding arboviral disease of variable severity characterized by the emergence of virus strains with greater fitness, epidemic potential and possibly virulence. To investigate the role of dengue virus (DENV) strain variation on epidemic activity we studied DENV-2 viruses from a series of South Pacific islands experiencing outbreaks of varying intensity and clinical severity. Initially appearing in 1971 in Tahiti and Fiji, the virus was responsible for subsequent epidemics in American Samoa, New Caledonia and Niue Island in 1972, reaching Tonga in 1973 where there was near-silent transmission for over a year. Based on whole-genome sequencing and phylogenetic analysis on 20 virus isolates, Tonga viruses were genetically unique, clustering in a single clade. Substitutions in the pre-membrane (prM) and nonstructural genes NS2A and NS4A correlated with the attenuation of the Tongan viruses and suggest that genetic change may play a significant role in dengue epidemic severity.