Xiaoxia Ren and Jason Rasgon talk in the lab

‘Accidental’ Virus Holds Promise for Battling Malaria

By Kurt Kleiner

It was scientific serendipity at its best.

Jason Rasgon, PhD, an assistant professor in the W. Harry Feinstone Department of Molecular Microbiology and Immunology (MMI), was having trouble with his experiment. He was infecting mosquito cells with Wolbachia bacteria, looking for a biological control agent to combat the spread of malaria.

But there was a problem with the cell line he was using as a control. Polymerase chain reaction (PCR) tests kept revealing an unexpected DNA band. At first Rasgon dismissed it as a meaningless artifact of the test. The band kept showing up, however, and finally Rasgon's team sequenced the DNA. They discovered that a virus called AgDNV was infecting the mosquito cells.

Now Rasgon thinks that this accidental virus might be just the weapon he needs to fight Anopheles gambiae, the primary transmitter of malaria in sub-Saharan Africa.

The discovery is significant because until now, there was no obvious biological control agent for Anopheles gambiae. Rasgon was working with Wolbachia because it infects many other insects, including other kinds of mosquitoes, and he hoped to figure out how to get it to infect Anopheles.

Instead, he ended up with a naturally occurring infectious agent that could provide a new weapon. The finding is surprising because researchers in the past had tried to infect Anopheles gambiaewith other strains of the virus taken from other insects but gave up when the mosquito proved largely immune.

Since they found the virus, Rasgon and his colleagues, Egbert Hoiczyk, PhD, an MMI assistant professor, and Xiaoxia Ren, PhD, a postdoctoral associate in Rasgon's lab, have shown that the virus will infect mosquito larvae, and that the virus is transmitted to the adult.

The trick now is to figure out how to use the virus to control malaria. One approach is to try to make the virus more deadly to the mosquito, probably by engineering in a toxin. To be most effective, Rasgon would like to use a "time bomb" approach, making the virus kill the mosquito at about 10 days old.

That's before the adult is capable of passing on the malaria infection, which happens when it is 14 days old. But it still gives the mosquito time to breed, lay virus-infected eggs, and further infect the water that it lays the eggs in.

Another approach would be to engineer the virus so that it interfered in some way with the mosquito's ability to nurture or pass on the Plasmodium parasite that causes malaria.

But Rasgon says a number of problems have to be overcome. First, he still needs to understand how the virus infects and affects the mosquitoes. For instance, it isn't consistently infective, with some mosquitoes heavily infected and some very lightly infected.

Next will be figuring out how to engineer the virus to be lethal at just the right time. Rasgon says the work will take time.

"We're talking years, not months," he says.

A paper describing the work was published August 22 online in the open access journal PLoS Pathogens.