ZIKA, DENGUE: Deprive the mosquito of its protection against infection

Indeed, to be able to transmit these infections, mosquitoes must be able to survive them. And Aedes aegypti mosquitoes do not succumb to these viruses when infected and continue to move and feed normally. They thus remain capable of transmitting their viral loads to humans. These researchers have just discovered the key role of the Argonaute 2 protein which allows them to survive infections.

Deprive mosquitoes of their protection mechanism against infection

This discovery represents a significant advance in the understanding of mosquito biology. It also gives hope for a strategy which would aim to deprive the mosquito of its defenses when it is infected by certain viruses, which would mechanically reduce their transmission to humans. The research also answers a long-standing question.

“Researchers have long wondered why mosquitoes don’t get sick when infected with these viruses. Our work solves the mystery and suggests a potential new strategy for vector-borne disease control,” comments one of the study’s lead authors, George Dimopoulos, professor of molecular microbiology and immunology at the Bloomberg School.

Aegypti mosquitoes transmit arboviruses, themselves transmitted by arthropods, including dengue virus, yellow fever virus, Zika virus, chikungunya virus and Mayaro virus. Each year, these pathogens sicken millions of people around the world, killing tens of thousands. There is no antiviral treatment for any of these viruses. Currently, a vaccine is available against the yellow fever virus. A dengue vaccine is approved by the US Food and Drug Administration (FDA) for people ages 6 to 16 who have had dengue. Among the main methods of controlling diseases transmitted by aegypti mosquitoes include the use of insecticides but with limited effectiveness and the risk of insecticide resistance.

Aegypti mosquitoes are themselves resistant to infection : they are in fact effective vectors of arborviruses because they can undergo significant infections by these viruses without their overall ability to reproduce being affected – what biologists call “fitness”. If mosquitoes’ fitness was altered, they would likely have developed strong defenses against these pathogens. Instead, they benefit from a balance

” live and let live “

which allows them to carry a moderate viral load without apparent adverse effects.

The role of Argonaute 2 (Ago2) is deciphered for the first time with this study. This is a protein that, in mosquitoes, regulates an important antiviral mechanism known as the small interfering RNA (siRNA) pathway, which works by recognizing and destroying viral RNAs. In other words,

  • Ago2 helps protect the mosquito against infections.

  • deprived of the Ago2 gene, the siRNA pathway is impaired, arborvirus infection becomes more severe, and the ability of mosquitoes to transmit these viruses is significantly reduced, as mosquitoes become ill, feed less, and die within a few days.
  • this increased mortality is caused not only by an impairment of the siRNA antiviral pathway, but also by defects in other processes also dependent on Ago2: DNA repair and autophagy, the fundamental process of elimination of cellular waste;
  • Ago2-deficient mosquitoes exposed to arboviruses develop “hyper-infections,” exhibit significant DNA damage, and suffer from accumulation of molecular waste.

Towards a new strategy for controlling arboviral diseases? This would involve manipulating mosquitoes so that arbovirus infections trigger the loss of their tolerance mechanisms, notably via the inhibition of Ago2.

“This biology of mosquito susceptibility and tolerance to infection provides an interesting area of ​​exploration for other pathogens,” the authors add, “for example, mosquitoes that transmit malaria parasites could also be altered so as to become ill and succumb to infection.”

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