Reverse Genetics and the Study of Dengue Virus

Dengue virus infection causes the most important arthropod-borne disease of humans. Currently, there are no dengue vaccines or antiviral therapies in clinical use, although their development is a global health priority. Using a technique known as ‘reverse genetics’, the dengue virus RNA genome can be manipulated, either by the introduction of specific mutations or the deletion and/or substitution of entire genes. This has led to the production of novel recombinant viruses that have potential as vaccines and the production of noninfectious viral subgenomes (termed replicons) useful for drug screening. Reverse genetics is also an invaluable tool for studying the role of dengue virus RNA elements and proteins in replication and pathogenesis. This review describes the contribution of reverse genetics to dengue virus research to date, highlighting the potential use of this technology in the development of effective control measures against dengue in the future.