Scientists from the University of Pittsburgh Center for Vaccine Research have discovered how a mosquito-borne virus “hijacks” a cellular regulatory system, suppressing immunity in the host.

Eastern equine encephalitis virus (EEEV) is a rare but deadly disease transmitted to humans by the bite from an infected mosquito.

The Centers for Disease Control and Prevention (CDC) estimates that between five and 30 cases are reported annually, and that these are most common in the Atlantic and Gulf States.

EEEV causes swelling in the brain, characterized by the sudden onset of headache, high fever, chills and vomiting. Patients can quickly become disoriented, suffer seizures and fall into a coma.

The fatality rate is between 30-70% – the highest of any North American mosquito-borne virus – and survivors are often left with significant brain damage.

The carrier mosquito is typically found in swampy areas that are not highly populated. However, the researchers say that in recent years, carriers were identified in more common mosquitos in Massachusetts. This prompted widespread insecticide spraying, curfews and the cancellation of many outdoor events.

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Discovering how the EEEV evades detection by the body’s immune system offers hope for a future vaccine, scientists say.

Publishing their findings in the journal Nature, the researchers explain how the virus evades the body’s normal immune response and spreads easily to the host’s neurological system, causing overwhelming disease.

Senior author William Klimstra, associate professor at Pitt’s Center for Vaccine Research, explains that EEEV carries ribonucleic acid (RNA) in its genes.

The researchers discovered that EEEV has evolved a binding site in its RNA that fits into a small piece of RNA (called microRNA) in the host’s cells. MicroRNAs are usually produced by the host to regulate its own cellular processes.

Once bound to the microRNA in cells involved in sparking an immune response in humans, it restricts its own replication. The virus can thus evade an immune response, as the cells are “blind” to its presence, and it can replicate unchallenged.

Prof. Klimstra adds:

Anytime you understand how a virus causes a disease, you can find ways to interrupt that process. And this discovery is particularly exciting because it is the first time that anyone has shown a virus using this particular strategy to evade its host’s immune system and exacerbate disease progression.”

Working in the laboratory, Dr. Klimstra and his team created a mutant variant of the virus, without the microRNA binding site. This proved to them that the binding was crucial to the virus evading detection.

The scientists also noted that without the binding site, the host was able to mount an effective immune response against the virus.

Looking forward, Dr. Klimstra hopes this discovery will lead to a vaccine and improve treatment options for infected patients. The research may also have implications for other diseases, including West Nile virus, dengue, rhinovirus and SARS.

He explains:

Viruses are constantly evolving and changing. However, the genetic sequence that allows EEEV to bind to our microRNA has persisted. We find it in samples from the 1950s, which indicates tremendous evolutionary selection pressure to maintain this mechanism.”

He adds that ultimately, their “results suggest that the mutant virus could be used as an EEEV vaccine and that microRNA blockers could have potential for use as a therapeutic treatment for EEEV-infected patients who currently can be treated only with supportive care.”