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Pitt Researchers Make Discovery About Deadly Mosquito-Borne Virus

You might not have ever heard of eastern equine encephalitis virus (EEEV) — it only affects five to 30 people in the United States annually — but it kills about half the people it infects, doesn’t have a cure and is becoming more common.

That’s according to William Klimstra, who, along with other University of Pittsburgh researchers, has made a major discovery that could lead to possible treatment for and prevention against the mosquito-borne virus.

The researchers have discovered that EEEV uses a never-before-documented mechanism to “hijack” one of its host’s cellular regulatory systems in an effort to suppress immunity.

Unlike other viruses, which continually replicate themselves, EEEV restricts its own replication using a microRNA-binding site, which can fool the human body.

Klimstra said the technique prevents the immune system from detecting and attacking the virus, so it travels to the brain without warning.

“The advantage that the virus gains from this is that when it gets into the brain, the brain hasn’t had any signal from the peripheral tissues that they are infected,” Klimstra said. “So the brain is essentially unprotected when the virus gets there and that’s why the disease is so severe.”

The researchers created a mutant version of the virus without the microRNA-binding site and found that the host’s -- in this case mice -- immune system was able to attack the mutant version.

The virus might be rare now, but Klimstra said that could not be the case for long.

“Typically the virus is maintained in a cycle between birds and a swamp mosquito that people aren’t very commonly exposed to, but in the last few years it’s been found more and more in mosquitos that inhabit urban environments and prefer to feed on people,” Klimstra said. “So there’s concerns from a number of different areas in terms of the potential for increased cases.”

EEEV causes inflammation of the brain, resulting in the sudden onset of headache, high fever, chills and vomiting.  It can progress quickly to disorientation, seizures and coma.

The virus has a 30 to 70 percent fatality rate, but those who do survive usually suffer substantial brain damage.

Klimstra said they hope this discovery will help researchers develop vaccines and treatments for the virus.

“The virus where we’ve deleted the binding sites for the microRNA, that virus is actually a natural vaccine vector because it’s naturally attenuated, it stimulates a much better immune response than the wild-type virus does, and something that we haven’t mentioned yet is that it is also incapable of infecting a mosquito,” Klimstra said.

He said this is important because it shows that the vaccine won’t spread from an immunized person to someone else.

He said there is also potential to create a treatment by purifying high levels of the microRNA and administering them to infected people to block virus replication.