Scientists have identified the critical role of the Argonaute 2 protein in Aedes Aegypti in resisting viruses such as dengue, yellow fever, and Zika. This discovery could help to reduce mosquito-to-human virus transmission. Infected Aedes Aegypti mosquitos are unaffected, allowing them to spread viruses to humans.

The findings, published in Nature Communications, shed light on mosquito biology and propose a strategy for weakening Aedes Aegypti's defenses when infected with a virus. Instead of increasing mosquito resistance, this approach may make them more susceptible to viruses, reducing their ability to transmit disease.

Study senior author George Dimopoulos, PhD, a professor in the Johns Hopkins Malaria Research Institute and in the Bloomberg School’s Department of Molecular Microbiology and Immunology said,

“Researchers have long wondered why Ae. Aegypti mosquitoes don’t get sick when they are infected by these viruses—our findings effectively solve this mystery and suggest a potential new mosquito-based disease control strategy that merits further study.”

The study's lead author, Dr. Shengzhang Dong, a senior research associate in the Bloomberg School’s Department of Molecular Microbiology and Immunology, investigated arborvirus infections responsible for millions of global illnesses and deaths annually. No antiviral treatments exist for these viruses, except a yellow fever vaccine and a limited-use dengue vaccine. Controlling Ae. Aegypti mosquitoes, potent arborvirus vectors, relies mainly on insecticides, facing resistance issues.

Mosquitoes maintain fitness despite viral infections due to a live-and-let-live balance. Researchers found that mosquitoes lacking Argonaute 2 (Ago2) weakened siRNA defense, intensified arborvirus infections, and reduced transmission rates. Impaired DNA repair and autophagy processes also contributed to increased mortality.

The discovery could lead to a new method for controlling arborviral diseases by engineering mosquitoes to lose tolerance mechanisms, causing rapid extinction of arborvirus-carrying mosquitoes.

“The biology of mosquito susceptibility and tolerance to infection is an interesting area of exploration for other pathogens as well,” says Dimopoulos. “For instance, mosquitoes that transmit malaria parasites could perhaps also be engineered to become sick and succumb to infection.”

Dimopoulos and his research group are now exploring possible ways of engineering Ae. Aegypti to test this possible new disease-control strategy.