The bait molecule attracts lethal mosquito-borne viruses from the mind

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The Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne virus that, in the worst case scenario, can infect the brain and become fatal. It’s notoriously difficult to treat, but now scientists have discovered the protein it binds to – and created a deceptive molecule that pulls the virus away from the brain.

VEEV originally comes from horses and is known to spread to humans through mosquito bites. Patients usually experience symptoms such as a high fever and headache. In the most severe cases, however, it can cross the blood-brain barrier and cause encephalitis. At this point it becomes potentially fatal in about a quarter of patients.

VEEV outbreaks have been reported in Central and South America since 1938. However, since it is a mosquito-borne disease, it is likely that they will continue to spread as the planet warms. New drugs and treatments are needed to keep the lid on.

“This virus can infect many species of wild mammals and leaps from animal to human via mosquitoes every few years, causing thousands of infections and many deaths,” said Michael S. Diamond, lead author of the new study. “There are concerns that with global warming and population growth, we will have more outbreaks.”

Viruses are usually known to attach to a specific protein on the surface of cells and invade in this way. For the study, researchers at the Washington University School of Medicine in St. Louis set out to first identify the protein VEEV targets.

Using a modified version of the virus that is infectious but does not cause disease, the team looked for the key protein. They used the CRISPR gene editing tool to systematically turn off genes in cultured mouse neurons until they found a batch that VEEV could not infect.

The missing gene, which was coding for a protein called Ldlrad3, and the team verified its significance by adding the gene back in – sure enough for the virus to catch on again. Follow-up tests in human cells lacking the human version of the gene showed that the same process works for us too.

With a goal in mind, the researchers then began working on a way to fight back. The mechanism is pretty clever – they used a piece of protein to create a “lock handle”. Some of the viruses would naturally cling to these instead of neurons, making them vulnerable to the immune system.

To test this, the team injected groups of mice with VEEV, either through the skin like a mosquito bite or directly into the brain, and then treated them with either the bait grip or a placebo. Treatments were given either six hours before or 24 hours after infection.

The results were pretty stark. Every single mouse given the placebo died in less than a week, while nearly all given the bait survived. The only exceptions were two of the 10 mice in the group that received the brain injection of the virus.

The team says the ultimate goal is to develop a drug that uses the deception molecule to slow the spread of VEEV during outbreaks. That is, it is very early to do research and a lot more testing needs to be done before any human studies can take place – although there is, of course, no guarantee that the same results will be achieved.

The research was published in the journal Nature.

Source: Washington University in St. Louis

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