Eastern equine encephalitis virus (EEEV) is a grim diagnosis: one in three people infected with the mosquito-borne disease will die within two weeks, and survivors face debilitating, long-term mental and physical impairments.  

Researchers led by professor of virology Kylene Kehn-Hall at Virginia Tech’s Virginia-Maryland College of Veterinary Medicine received a total of $3.3 million from the Department of Defense to study models of how EEEV changes the brain.  

EEEV affects a small number of people every year — in 2020, 13 people in the United States were diagnosed — but it is a serious disease. There are no specific antiviral treatments available, and the virus has a mortality rate between 30 and 80 percent. EEEV can cause neurologic disease, which can permanently damage the brains of survivors.

"We're most interested in individuals who survive the infection; there's a 50 to 90 percent chance of long-term complications. These complications can be things such as seizures, intellectual disabilities like memory issues, and behavioral and emotional issues. We are trying to understand why that's happening and ways to prevent it,” said Kehn-Hall.  

For the past 10 years, Kehn-Hall has studied Venezuelan equine encephalitis virus, EEEV’s far milder cousin. To study the lasting effects of EEEV, she will collaborate with researchers from Virginia Tech, George Mason University, and the U.S. Army Medical Research Institute of Chemical Defense.  

As part of one grant, Kehn-Hall and her collaborators will develop a mouse model of EEEV's lasting neurological effects in an attempt to understand the underlying biology and what is happening on the molecular level. They will work toward identifying neurological pathways in hopes of identifying therapeutics that can reverse the damage.  

While other studies have examined models of how the virus kills, Kehn-Hall, along with Barney Bishop of George Mason University and the veterinary college’s Michelle Theus, associate professor of molecular and cellular neurobiology, are looking at survivors.  

"Of course we want to prevent death, but we also want to prevent people from having disabilities for a long period of time, even the rest of their lives. If we can model what's contributing to these changes, then we can intervene early in such a way that we can prevent that damage from occurring,” said Kehn-Hall.

As part of the second grant, Kehn-Hall will work with Theus and Hehuang “David” Xie, professor of epigenomics and computational biology. Co-investigators will include Xiaowei Wu, assistant at Virginia Tech College of Science’s Department of Statistics, and John McDonough and Erik Johnson of the U.S. Army Medical Research Institute of Chemical Defense.

The team will compare data regarding traumatic brain injury, organophosphate nerve agent, and encephalitic alphaviruses, which include Venezuelan, eastern,, and western equine encephalitis viruses.  

“We will investigate the association between gene expression profiles and disease phenotypes,” Xie said.

“My team’s work on traumatic brain injury draws many parallels to what happens to the brain when it’s infected with viruses,” said Theus. “The comparative work underway will help us understand the common pathologies between these traumatic events and whether select regions of the brain are similarly affected. We hope to expand what we have learned in traumatic brain injuries to injuries associated with this type of biological threat.”

They will look for gene expression and cellular changes in mice exposed to Venezuelan and eastern equine encephalitis virus.

Epileptic seizures are already known to be a common outcome associated with traumatic brain injury, equine encephalitis viruses and nerve agents. ”We believe there is a common event that occurs in the development of seizures that can be targeted therapeutically,” said Theus.

Because the development of seizures is already known, the researchers will focus on the hippocampus and changes in neurons.

Through comparing data from encephalitic alphaviruses, organophosphate nerve agent, and traumatic brain injury, they aim to better understand the similarities between these conditions and thus identify potential medical treatment.  

There is no approved human vaccine for EEEV, but there is an equine vaccine administered yearly. Though EEEV may be deadly and have devastating, lasting effects, the low number of annual cases means there isn’t much incentive for humans to get vaccinated. Because of this, therapeutics are a better option than vaccines.  

Through developing therapeutics, researchers can help those who are fighting this virus and its long-term effects. 

Written by Sarah Boudreau M.F.A. '21, a writer with the Virginia-Maryland College of Veterinary Medicine