Disease-Proofing Mosquitoes

Zach Adelman ’96 works to keep the tiny pests from spreading deadly diseases. 

By Doug McInnis

Scientists have sent astronauts to the moon and built artificial hearts, but they have never been able to rein in the lowly mosquito, delivery agent for some of the deadliest viruses on earth. Now Zach Adelman ’96 and his research team at Virginia Tech are searching for the genetic keys that turn mosquitoes into carriers of the viruses that cause dengue and yellow fever.

Both fevers have become major public health concerns, according to the World Health Organization. Cases of both have increased dramatically in recent decades, due to deforestation, urbanization, and climate change. There are an estimated 200,000 cases of yellow fever worldwide each year, resulting in 30,000 deaths. There may be as many as 50 million dengue infections worldwide every year.

There is no known cure for either dengue or yellow fever, and care for severely ill patients is not available in poor areas. The only way to fight these viruses is to combat the disease-carrying mosquitoes.

Finding the Right Genes

The immune system of most mosquito species allows them to naturally resist such viruses. But a handful of species lack resistance. When these vulnerable mosquitoes get infected, they don’t get sick themselves. Instead, they serve as virus incubators, and, when they bite, they pass on the virus.

If researchers can determine the genetic differences between mosquitoes that merely annoy us and those that transmit disease, they might devise a solution. Adelman’s lab is studying which mosquito genes are important in warding off viruses. “Right now, it’s a black box,” says Adelman, associate professor of entomology. “We know how things work only in general and very vague terms. If we find out more about what’s going on, we could have a better idea of how to implement some kind of control. Maybe there are 10 genes involved or 100. We just don’t know.”

The mosquito has roughly 15,000 genes, a number too daunting to take a one-by-one approach. Adelman and his team are testing some 100 to 200 of the most likely candidates. Each test takes from a couple of weeks to several months to conduct.

Using a novel method he and his collaborator developed, Adelman engineered the mosquitoes so that their eyes fluoresce a bright green when a gene involved in immune function is switched off.

“We would expect that when all genes are working normally (eyes not green) the mosquitoes could transmit viruses. By switching off an important gene they would still be able to transmit,” Adelman says. “That tells us if the gene is involved in this immune pathway. Then we hatch a new batch of mosquitoes and do it again, and again, and again.”

Exploring the Possibilities

It may be that mosquitoes resistant to these viruses have the same immune-function genes as their virus-toting counterparts. In that case, the difference may be that immune mosquitoes have certain immune genes switched to the “on” position, while other mosquitoes have these immune genes turned off. Or it may be that the immune mosquitoes simply have different genes. “We have no idea,” says Adelman.

Adelman could not use the mosquito’s own genes as a weapon until scientists sequenced the genomes of the handful of mosquito species that transmit viruses such as yellow fever, dengue, and West Nile. “There were a lot of questions we couldn’t ask until we had the genome,” says Adelman.

Now he spends plenty of time in the lab trying to figure out which mosquito genes confer immunity. The answer could someday help save lives. “We know of a couple of genes so far,” he says. “We’re just trying to find more, so we can understand how mosquitoes defend themselves against these viruses. Only then will we be able to understand what turns a simple pest into a potential killer.”