Genetics of dengue epidemics

Abstract

Dengue is an acute mosquito-borne viral disease widespread throughout tropical regions. Cyclical epidemics on top of high endemic dengue incidence strain many healthcare systems. While low population immunity to the four dengue viruses (DENVs) is often cited as the cause of epidemics, not all new DENV introductions have caused epidemics. Moreover, the role of DENV genetics in epidemic emergence has remained understudied. This review examines how genetic changes affect DENV fitness and links specific epidemics to these changes, focusing especially on those where the biological functions altered by the genetic changes have been experimentally defined. Most of these changes were in the nonstructural genes and untranslated regions of the DENV genome, rather than in the commonly sequenced envelope (E) gene; many genetic traits of DENVs from past epidemics could have been missed through E gene sequencing alone. Our review calls for a systematic approach to understand the genetics of dengue epidemics and to form a foundation for early epidemic warning systems.

Keywords: dengue; epidemics; epidemiology; evolution; genetics; mutations.