Researchers from the Johns Hopkins Institute for Malaria Research at the Johns Hopkins Bloomberg School of Public Health have made an important discovery about Aedes aegypti mosquitoes, a discovery that could one day lead to better ways to reduce the transmission of dengue fever and yellow fever from mosquitoes to humans, Zika viruses and other harmful and sometimes deadly viruses.
The researchers published the results of their study in the journal Nature Communications on Sept. 18.
The secret is in protein
Aedes aegypti mosquitoes do not succumb to viruses when infected and continue to move and feed normally, and as such infected mosquitoes can transmit their viral loads to humans.
The researchers discovered that the Aedes aegypti protein called ergonut 2 plays a key role, through many biological mechanisms, in keeping mosquitoes healthy and active despite these infections.
The discovery represents a major advance in understanding the biology of mosquitoes, and hints at a strategy aimed at closing the defenses of Aedes aegypti when infected with certain viruses, thereby killing mosquitoes and reducing the transmission of those viruses by Aedes aeres auges to humans.
Rather than making mosquitoes more resistant to viruses, the discovery opens up a potential avenue for making mosquitoes more susceptible and less tolerant of infection with the virus, potentially impairing their ability to transmit the disease.
New discovery opens up potential pathway to make mosquitoes more susceptible to infection and less tolerant of the virus (Shutterstock)
Study senior author Professor George Dimoupolios at the Johns Hopkins Malaria Research Institute said: "Researchers have long wondered why Aedes aegypti mosquitoes don't get sick when they are infected with these viruses.
Aedes aegypti and viral load
Aedes aegypti mosquitoes transmit a number of pathogenic viruses, including dengue virus, yellow fever virus, Zika virus, chikungunya virus and Mayarovirus virus.
Every year, these viruses infect millions of people around the world, killing tens of thousands, and there are no antiretroviral treatments.
The methods of combating Aedes aegypti diseases are the use of pesticides, which have had limited success.
Aedes aegypti mosquitoes are an effective vector of viruses because they can withstand large infections without bearing the costs of their overall ability to reproduce, what biologists call "fitness."
Researchers examined the role of the argonut-2 gene, a protein that acts in mosquitoes as part of an important antiviral mechanism (Shutterstock).
In the new study, Dimoupolios and his team examined the role of the argonut-2 gene, a protein that works in mosquitoes as part of an important antiviral mechanism known as the small interfering RNA pathway (SERNA), which works by recognizing and destroying viral RNA.
According to a press release from the Johns Hopkins School of Public Health, the researchers found that when Aedes aegypti mosquitoes lack the Argonaut 2 gene, the small interconnecting RNA pathway is disrupted, the virus infection in mosquitoes becomes more severe, and the ability of mosquitoes to transmit these viruses decreases sharply, as they get sick and feed less, and often die within days.
The scientists showed that this increase in mortality is due not only to a weakening of the antiviral pathway, but also to defects in two other processes based on Argonut 2, the first of which is DNA repair, and the other is the removal of basic waste called autophagy in which mosquitoes that are deficient in Argonot 2, exposed to viruses, are left with excessive infection, extensive DNA damage, and the accumulation of molecular waste in their dying cells.
Mosquito susceptibility biology and susceptibility to infection An interesting area for exploring pathogens (Shutterstock)
Disease Control Strategy
Apart from shedding light on an important aspect of Aedes aegypti biology, the findings point to a potential new strategy to combat viral diseases.
Infection with pathogenic viruses leads to loss of tolerance mechanisms, possibly by inhibiting Argonut-2 in Aedes aedes aedes (aedes) carrying viruses, so mosquitoes die quickly, while the much larger number of non-pathogenic mosquitoes are not affected.
"The biology of mosquito susceptibility and tolerance is an interesting area for exploring other pathogens as well, for example mosquitoes that transmit malaria parasites may be modified to become sick and succumb to infection," says Dimopolios.
Dimoupolios and his research group are now exploring possible ways to engineer Aedes aedes to test this potential new strategy for disease control.