Can antiviral agents help mosquitoes’ immune systems fight the dengue virus?

Dengue virus (DENV) is spread by the Aedes aegypti mosquito or the yellow fever mosquito, a species that remains a source of frustration for mosquito control agencies, medical entomologists, and ecologists. A virus that poses a public health risk to up to 100 million people worldwide each year, dengue virus is particularly prevalent in South and Central America, sub-Saharan Africa, southern Asia, the Pacific islands, and has reached Florida via inbound Traveler.

University of Florida researchers at the Institute of Food and Agricultural Sciences (UF / IFAS) have published a study showing an evolution in the species’ ability to fight dengue virus by exposure to antiviral agents.

Can the dengue virus be prevented with antiviral agents such as antibiotics or vaccines? Before considering this step, scientists at the University of Florida are looking more closely at whether the mosquito’s immune system can be manipulated enough to fight the virus as a control method.

Ultimately, UF / IFAS scientists are trying to find a way to prevent Aedes aegypti from contracting the dengue virus.

In a new one to learn, Scientists at UF / IFAS Florida Medical Entomology Laboratory (UF / IFAS FMEL) investigated how the immune system of the Aedes aegypti mosquito reacts when it is exposed to two antiviral agents. Scientists gained much-needed insight into the physiology of the species, its immune system response to agents against the dengue virus, and their next steps in developing new control strategies to keep people safe from the disease.

“We wanted to find out what could help or stop the virus from multiplying in the mosquito so we could use the process to prevent humans from contracting the disease,” said Chelsea Smartt, Co-author of the study and Associate Professor of Molecular Biology and Biochemistry at UF / FMEL in Vero Beach.

To achieve this goal, the researchers wanted to understand the role of autophagy in Aedes aegypti mosquitoes. Autophagy occurs at the cellular level in organisms. It is the body’s method of cleansing damaged cells in order to regenerate new, healthier cells. It’s getting less the likelihood of developing some diseases and extending their lifespan.

If infected, autophagy can destroy bacteria and viruses. It plays a role in immunity. Dengue infection has been shown to trigger the autophagy pathway, which increases viral replication in humans. “We’re trying to find a gene or molecule that makes a vaccine that could act as a control method for the mosquito to keep people from getting the disease,” said Smartt.

Ultimately, the purpose was to deliver the vaccine from a bait station that would attract the mosquitoes, Smartt said.

Autophagy is a signaling pathway that plays a role in maintaining cellular health and involves multiple interactions in the cell, said Tse-Yu Chen, lead author of the study published in Parasites & Vectors and a PhD student at UF / IFAS FMEL at the time of the study. “As scientists in the field view autophagy as a critical pathway involved in the replication of dengue virus in humans, I was interested in understanding the interaction between the autophagy pathway and the virus transmission cycle in mosquitoes,” said Chen, now a postdoc at Yale University. “The discovery by this route of an antiviral candidate that could stop the cycle of transmission would be an indication that the virus could be controlled at an earlier stage.

For the study, the scientists used two drugs that are commonly prescribed to fight infections in humans: rapamycin and 3-methyladenine. Previous research has shown that both affect the autophagy pathway in mammals. The researchers present the active substances to determine whether they activate or suppress the autophagy pathway in an Aedes aegypti cell line infected with the dengue virus. “Most research on mosquito-borne pathogens looks at the virus later in the infection cycle. We wanted to see what happens in the early stages of the infection to stop virus replication, ”said Smartt.

“If we could help the mosquito kill the virus before it replicates, the mosquito won’t be a sufficient vector to carry pathogens that cause disease in humans,” said Chen. “That is why it is important to concentrate on the autophagy path at an early stage. The drugs we used for the study are already established and more stable with the possible development of a mosquito vaccine. “

After a two day snapshot, the rapamycin treatment mixed into the mosquito cells blocked the virus’ ability to replicate. Scientists compared this finding to the control cells that were left untreated, Smartt said. “The experiment showed that some autophagy genes helped block the virus from replicating,” said Smartt. “These will be genes that can be studied as vaccine candidates in the future.”

“Autophagy plays an important role in mosquito dengue infection,” said Chen. “Although we still have to review the role of autophagy in the mosquito Aedes aegypti, we are confident that the cell data will confirm the existence of an interaction between autophagy, mosquito and the virus. We will continue to investigate the possibility of rapamycin as a mosquito vaccine and hopefully the good news will be out soon. “

Tse-Yu Chen, researcher.
Photo courtesy Chelsea Smartt

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