Researchers at Johns Hopkins University have characterized a virus that is infectious to Anopheles gambiae – the mosquito primarily responsible for transmitting malaria. According to the researchers, this virus could potentially be used to pass on new genetic information to A. gambiae mosquitoes to help control malaria, which kills over one million people worldwide each year.
Paratransgenesis, the genetic manipulation of mosquito symbiotic microorganisms, is being considered as a potential strategy to control malaria. Microorganisms associated with Anopheles mosquitoes could be manipulated to alter the mosquito’s ability to become infected with and transmit the malaria parasites, or reduce mosquito fecundity or lifespan. The researchers identified the first potential microorganism (A. gambiae densovirus; AgDNV) for paratransgenesis of the major malaria vector Anopheles gambiae. AgDNV is highly infectious to A. gambiae larvae, disseminates to adult tissues and is transmitted vertically to subsequent generations. Recombinant AgDNV was able to transduce expression of an exogenous gene (EGFP) in A. gambiae cells and mosquitoes. EGFP-transducing virions infected mosquitoes, expressed EGFP in epidemiologically relevant tissues and were transmitted to offspring in a similar manner to wild-type virus. AgDNV could be used as part of a paratransgenic malaria control strategy by transduction of anti-Plasmodium genes or insect-specific toxins in Anopheles mosquitoes, as well as an easy-to-use system for transient gene expression and RNAi for basic laboratory research.
AgDNV is a member of the Parvovirus family, a “densovirus”, which are quite common in mosquitoes and other insects, but do not infect vertebrates such as humans. Although AgDNV does not appear to harm the mosquitoes, the researchers determined it is highly infectious to mosquito larvae and is easily passed on to the adults. The discovery came about serendipitously while the research team was conducting experiments to determine whether Wolbachia bacteria could be used to infect A. gambiae mosquito cells. During the analysis, they noticed an “artifact” that appeared as an unexpected prominent band in the gel used to detect the bacteria. The virus could be altered to kill the mosquito or make A. gambiae incapable of transmitting malaria. To test the concept, the research team successfully used altered AgDNV to express harmless green fluorescent protein in the adult mosquitoes which could be easily spotted under the microscope. In theory, we could use this virus to produce a lethal toxin in the mosquito or instruct the mosquito to die after 10 days, which is before it can transmit the malaria parasite to humans. However, these concepts are still many years away from practical use.