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Breakthroughs

Dengue-Proof Mosquitoes

By Greg Rienzi
Illustration of a mosquito
George Dimopoulos is a professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health. He focuses on the development of novel malaria and dengue control strategies.

The tools of combat to control mosquito-borne diseases like dengue fever mostly fall into three groups: kill, repel, or prevent. People spray. Lay traps. Put up nets. Eliminate breeding grounds. We concoct whatever tactic necessary to disrupt interaction between humans and a 4-millimeter insect that Bill Gates famously described as the world's deadliest creature.

Molecular microbiologist George Dimopoulos and a team of Johns Hopkins researchers want to try a different approach: to disarm the mosquito from the virus. They attempted to re-engineer Aedes aegypti, the common mosquito species that spreads dengue and yellow fever, and essentially make it virus-resistant by giving the mosquito a more powerful immune system.

We need new approaches. Forty percent of the world’s population is at risk from dengue, which is most common in Southeast Asia and the western Pacific, and has been on the rise in Latin America and the Caribbean. Dengue continues to sicken an estimated 96 million people annually and kills more than 20,000, mostly children.

Mosquitoes get the virus by biting a dengue-infected human. The bug can then
pass on the disease to the next person it bites. But not all mosquitoes become infected. Just as a human fights off a viral infection, the mosquito has its own immune system that kicks in to fend off a foreign invader. Using genetic engineering, the researchers targeted the two genes that control this immune response and instructed them to be more active—but only immediately after a blood meal. Imagine a sexually transmitted
disease-blocking mechanism that switched on only when you have sex.

The results showed that the modified mosquitoes, which fed on dengue-infected blood, had significantly less virus, and the transmission-capable mosquito rate fell from 70 percent to 42 percent. While the modified mosquitoes suppressed dengue virus infection, they did not resist Zika or chikungunya, two other viruses carried by Aedes aegypti. “This finding teaches us something about the mosquito’s immune system and how it deals with different viruses. It will guide us on how to make mosquitoes resistant to multiple types of viruses,” Dimopoulos says.

Making mosquitoes completely resistant to a disease will be difficult, he says, but even reducing the infection rate by 30 to 40 percent could have a significant epidemiological impact. Further research is needed to make the virus-blocking mechanism more potent and/or turn on additional blocking mechanisms.

Dimopoulos, a professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, says the ultimate plan is to release the lab-created mosquitoes and have them supplant the wild population. But in addition to further tinkering with the infection-fighting component, the researchers have to develop a way to make the modified genes carry on to subsequent generations. They’ll do this through what is called gene drive, which promotes the inheritance of a particular gene so it can spread rapidly through a population. Later will come confined field trials where the modified mosquitoes are released in a net-covered shed to mate. The final trial phase will be open field release, most likely on an isolated island.

The approach has many advantages, Dimopoulos says. It’s environmentally conscious and cost-effective, and requires no active participation. Just release and let nature take its course. Dimopoulos reassuringly adds that he’s not setting up a cataclysmic sci-fi scenario where monster insects are being released into the environment. In the lab, the modified mosquitoes are as fit and flawed as the wild type. They don’t live longer. They’re not smaller or bigger, or better at transmitting other pathogens. They’re not more resistant to pesticides. “They’re basically the same mosquito. And ours produce slightly fewer eggs,” he says. “The biggest risk that I could see is that the [dengue virus] will grow a resistance to this blocking mechanism over time. And disease transmission will resume.”

Illustration of mosquitoes in a stylized pattern
Illustration above by Whitney Sherman; Illustration to the left by Mitch Blunt
Bill Gates once famously described mosquitoes as the deadliest creature in the world because of the diseases that they spread. Now, researchers are learning how to genetically alter the insect to make it resistant to spreading viruses like dengue fever.

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