In a new study, researchers have made a new discovery regarding Aedes aegypti mosquitoes, shedding light on a potential breakthrough in the battle against mosquito-borne viruses like dengue, yellow fever, and Zika (Figure 1). These viruses, often devastating and sometimes fatal for humans, are spread via Ae. aegypti mosquitoes, which remarkably remain unaffected by these pathogens. The research centers on a crucial Ae. aegypti protein, Argonaute 2, which plays a pivotal role in bolstering the mosquitoes’ resilience and continued mobility in the face of viral infections.
The findings represent a significant leap forward in our comprehension of mosquito biology. Moreover, they hint at a novel strategy – dismantling Ae. aegypti mosquitoes’ defenses upon viral infection. By rendering these mosquitoes less impervious to viruses, their ability to transmit diseases could be severely impaired, potentially curbing the virus’s spread to humans. This approach is distinct from the conventional practice of bolstering mosquito resistance to viruses.
Ae. aegypti mosquitoes are notorious for transmitting arboviruses, including dengue, yellow fever, Zika, chikungunya, and Mayaro viruses. Each year, these pathogens afflict millions of individuals globally, with tens of thousands succumbing to the diseases they cause. Currently, there are no antiviral therapies available for these viruses, except for a vaccine against yellow fever and a dengue vaccine for specific populations. Control methods primarily rely on insecticides, which have encountered limited success and led to the emergence of insecticide-resistant mosquitoes.
The research zeroes in on Argonaute 2 (Ago2), a critical protein that operates within Ae. aegypti mosquitoes as part of the siRNA pathway, a potent antiviral mechanism that identifies and destroys viral RNAs. In mosquitoes where the Ago2 gene is absent, the siRNA pathway is inhibited, rendering arbovirus infections more severe. Mosquitoes with compromised siRNA pathways become less capable of transmitting viruses, as they fall ill, reduce their feeding activity, and often perish within days.
This breakthrough research holds promise for advancing our strategies against mosquito-borne viruses. By targeting the vulnerabilities in Ae. aegypti mosquitoes, we may finally gain the upper hand in mitigating the transmission of these devastating diseases. Instead of focusing on making mosquitoes more virus-resistant, we may be on the brink of rendering them more susceptible, offering a glimmer of hope in our quest to thwart the spread of mosquito-borne viruses.
Journal article:Dong, S., et al. 2023. Aedes aegypti Argonaute 2 controls arbovirus infection and host mortality. Nature Communications.
Summary by Stefan Botha