Scientists have genetically modified mosquitoes in the lab to resist infection from dengue, a virus that each year effects around 96 million people globally and kills more than 20,000, mostly small children and the elderly.
The research published in the online journal PLOS Neglected Tropical Diseases, shows, at least in the lab, that the modification boosts the Aedes aegypti mosquito’s natural ability to fight dengue virus. This is a major first step toward suppressing the insect’s ability to spread the disease via its saliva.
The results could lead to a global effort to eliminate the threat of dengue. 40% of the world’s population is at risk from the virus, which is most common in Southeast Asia and the western Pacific. The Virus has also been increasing in Latin America and the Caribbean in recent decades.
“If you can replace a natural population of dengue-transmitting mosquitoes with genetically modified ones that are resistant to virus, you can stop disease transmission,” says study leader George Dimopoulos of the Malaria Research Institute at Johns Hopkins University. “This is a first step toward that goal.”
While the modified mosquitoes significantly suppressed the dengue virus infection but they did not resist Zika or chikungunya.
“This finding, although disappointing, 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,” says Dimopoulos, professor of molecular microbiology and immunology at Johns Hopkins’ Bloomberg School of Public Health. “ideally, you want a mosquito that is resistant to other viruses as well,” he says.
Mosquitoes are infected by feeding on blood from infected people and once the mosquitoes have the virus, they infect healthy people and pass the disease along.
Releasing them into the wild
Normal Aedes aegypti mosquitoes do have an immune response when exposed to dengue, but it is too weak to stop transmission. Dimopoulos and colleagues were able to manipulate the JAK-STAT pathway of the immune system, which regulates antiviral factors. The JAK-STAT pathway is involved in antiviral activity in humans as well.
The genetic modification resulted in fewer mosquitoes becoming infected. These experiments, however, didn’t lower the virus level in all mosquitoes to zero, which perplexed the scientists. More research is needed to understand if this level of virus suppression would be enough to halt disease transmission. They also are working to produce antiviral factors in the gut, which could induce an immune response and possibly confer resistance to other viruses.
The dengue-resistant mosquitoes live as long as normal mosquitoes, though they produce fewer eggs, most likely because the same mechanism involved in ramping up the immune system to fight dengue also plays a role in egg production.
“It’s likely if we turn this on in the gut we could have a much stronger effect, without compromising egg production,” Dimopoulos says.
In the near future the modified mosquitoes will be field tested in large cages to see if they can eventually, through interbreeding, supplant a population of wild mosquitoes with their increase immune abilities. .
“In this way, you could convert a disease-transmitting mosquito population to one that does not transmit disease,” Dimopoulos says.
Dimopoulos and other scientists are working on similar models in Anopheles mosquitoes that carry the parasite that causes malaria.
Source: Johns Hopkins University