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VERO BEACH, Florida – Can the dengue virus be prevented by using antiviral agents such as antibiotics or vaccines? Before considering this step, scientists at the University of Florida take a closer look at whether the mosquito’s immune system can be influenced enough to fight off the virus as a method of control.

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

In a new study, scientists at the UF / IFAS Medical Entomology Laboratory in Florida (UF / IFAS FMEL) examined how the immune system of the Aedes aegypti mosquito reacts when exposed to two antiviral agents. Scientists have gained much needed information on the physiology of the species, its immune system’s response to agents against the dengue virus, and the next steps to develop new control strategies to prevent people from contracting the disease. .

“We wanted to determine what might improve the replication of the virus in the mosquito or what might stop it so that we can use the process to prevent humans from being infected with 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 in organisms at the cellular level. It is how the body cleanses damaged cells to regenerate new, healthier cells. It reduces the likelihood of contracting certain diseases and prolongs 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 enhances virus replication in humans.

“We are trying to find a gene or a molecule that will make a vaccine that would serve as a method of mosquito control to prevent humans from contracting the disease,” said Smartt.

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

Autophagy is a pathway that plays a role in maintaining cellular health and involves multiple interactions within the cell, said Tse-Yu Chen, lead author of the study published in Parasites & Vectors, and a doctoral student at the time of study at UF / IFAS. FMEL.

“Because scientists in the field view autophagy as a crucial pathway that plays a role in dengue virus replication in humans, I was interested in understanding the interplay between the autophagy pathway and the cycle of virus transmission in mosquitoes, ”said Chen, now a postdoctoral associate at Yale University. “Finding an antiviral candidate in this pathway 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 commonly prescribed to fight infections in humans: rapamycin and 3-methyladenine. Previous research has shown that both influence the autophagy pathway in mammals. The researchers present the agents to determine whether they activate or suppress, respectively, the autophagy pathway in an Aedes aegypti cell line that has been infected with the dengue virus.

“Most of the 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 infection to stop viral replication,” he said. said Smartt.

“If we could help the mosquito kill the virus before it replicates, the mosquito will not become a sufficient vector to transmit pathogens that cause disease in humans,” Chen said. “This is why it is important to focus on the autophagy pathway at an early stage. The drugs we used for the study are already established and are also more stable in the eventual development of a mosquito vaccine. “

After a two-day snapshot, the rapamycin treatment mixed with the mosquito cells blocked the virus’s ability to replicate. Scientists compared this finding to control cells that were not processed, Smartt said.

“Experience has shown that a few autophagy genes help block virus replication,” Smartt said. “These will be genes to study for the future as a vaccine candidate.”

“Autophagy plays an important role in dengue infection in mosquitoes,” Chen said. “Although we have yet to verify the role of autophagy in the Aedes aegypti mosquito, we are convinced that cellular data supports the existence of an interaction between autophagy, mosquito and virus. We will continue to assess the possibility of rapamycin as a mosquito vaccine, and hopefully the good news will come soon. “


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