Venezuela’s horse encephalitis virus (VEEV) is a mosquito-borne virus that, in the worst case, infects the brain and becomes a deadly virus,media New Atlas reported. It is known to be difficult to treat, but now scientists have discovered the protein it adsorbed — and used it to create a bait molecule that draws the virus out of the mouse’s brain.
VEEV originated in horses and is known to be transmitted to humans through mosquito bites. Patients often experience symptoms such as high fever and headache, but in the most severe cases it can cross the blood-brain barrier, causing encephalitis. By then, it could be a potentially fatal disease for a quarter of patients.
Outbreaks of VEEV have been reported in Central and South America since 1938, but as a mosquito-borne disease, they are likely to become more widespread as the planet warms. New drugs and treatments will be needed to control it.
“The virus can infect many species of wild mammals, and every few years it jumps from animals to humans through mosquitoes, causing thousands of infections and many deaths,” said Michael S. Diamond, senior author of the new study. “There are fears that with global warming and population growth, there will be more outbreaks.”
Typically, viruses are known to adhere to specific proteins on the cell surface and enter the body in this way. So for the study, researchers at Washington University School of Medicine in St. Louis first set out to identify VEEV’s target protein.
The team screened key proteins using an improved version of the virus that is contagious but does not cause disease. Using CRISPR gene-editing tools, they systematically knocked out genes from neurons in cultured mice until they found a batch of genes that VEEV could not infect.
The missing gene encodes a protein called Ldlrad3, and the team tested its importance by adding the gene back — and sure enough, the virus was able to “get on its feet” again. Follow-up tests in human cells that lack human versions of the gene have shown that the same process can work in humans.
With the goal, the researchers began to study ways to fight back. The mechanism is pretty clever — they make a “bait handle” out of a protein. Some viruses are naturally attached to it, rather than neurons, making them vulnerable to attacks by the immune system.
To test it, the team injected a group of mice with VEEV, either through the skin like a mosquito bite, or directly into the brain, and then treated them with a “bait handle” or a placebo. Treatment is done 6 hours before or 24 hours after infection. The results are quite stark. Each mouse that received a placebo died within a week, while almost all of the mice that received the “bait handle” survived. The only exception was two of the 10 mice in the group that received the brain-injected virus.
The team says the ultimate goal is to develop a drug that uses bait molecules to slow the spread of VEEV during an outbreak. Still, the study is at a very early stage, and more tests are needed before human studies can finally be conducted — and, of course, there is no guarantee that the same results will be seen.
The study was published in the journal Nature.