Densoviruses for control and genetic manipulation of mosquitoes

Mosquito densoviruses (MDV) are parvoviruses that replicate in the nuclei of mosquito cells and cause the characteristic nuclear hypertrophy (densonucleosis) that gives them their name. Several MDV that differ in pathogenicity both in vitro and in vivo have been isolated. MDV have a number of features that make them potentially attractive as biological control agents for mosquito-borne disease. They are nonenveloped and relatively stable in the environment. They are highly specific for mosquitoes and they infact and kill larvae in a dose dependent manner in the aqueous larval habitat. Infected larvae that survive to become adult mosquitoes exhibit a dose-dependent shortening of lifespan and many do not survive longer than the extrinsic incubation period for arboviruses. Thus they may have a significant impact on transmission of pathogens. Infected females can transmit the virus vertically by laying infected eggs in new oviposition sites. Studies on how MDV affect populations are relatively limited. Population cage studies suggest that they will persist and spread in populations and limited field studies have shown similar preimaginal mortality in wild populations to that seen in laboratory studies. The availability of infectious clones of MDV genomes allows the development of densovirus vectors for expressing genes of interest in mosquito cells and mosquitoes. Recently short hairpin RNA expression cassettes that induce RNA interference have been inserted into densovirus genomes. These expression cassettes should be useful for both research and disease-control applications.