The deadly Eastern equine encephalomyelitis virus is a

A New Hampshire resident recently died from Eastern Equine Encephalitis Virus (EEE virus), which is spreading in five New England states.

Neither the virus nor the disease are new and remain rare. But the pathogen's ability to cause devastating infections in some people while showing hardly any symptoms in others continues to puzzle scientists.

Virologist Jonathan Abraham, associate professor of microbiology at the Blavatnik Institute of Harvard Medical School and infectious disease specialist at Brigham and Women's Hospital, has studied the virus in detail. In studies published in Nature In 2021 and 2024, Abraham and his team mapped the structure and behavior of the cell receptors—the entrances on the surface of cells—that allow the EEE virus and similar viruses to infect their hosts and cause damage.

Abraham spoke with News from Harvard Medicine about the known and unknown aspects of the EEE virus and the course of the recent outbreak.

News from Harvard Medicine: Do we have any idea what proportion of people bitten by an infected mosquito later develop symptoms of the disease?

Abraham: Not really, because we are not currently conducting any tests to determine whether someone is contagious. Many infected people develop mild symptoms such as headaches, fever and general malaise, but they usually go undiagnosed because they never seek medical treatment.

About 2 percent of those affected develop encephalitis, a form of brain infection that is the most dangerous complication of the disease. Up to a third of those affected die from it. And many survivors develop permanent symptoms, including seizures and paralysis, and may require long-term care in a nursing home. So while it is a relatively rare complication, the consequences can be devastating.

HMNews: Are there certain people who are at higher risk for symptomatic infections and encephalitis due to their age or health problems?

Abraham: Yes. People under 15 and people over 50 tend to develop more severe infections. There are no good data on the impact of immune status on the risk of severe disease, but there is some evidence that people with weakened immunity, such as transplant recipients, can have very severe infections.

I would also like to point out that much of the brain damage we see in this disease is not only caused directly by the virus, but also occurs as a side effect of the widespread inflammation of the brain that is trying to contain the infection.

HMNews: How are people who show symptoms and test positive for the virus currently being treated?

Abraham: There is really no specific treatment other than general supportive care. Some intravenous immunoglobulins have been used, but there is no convincing evidence that they make a significant difference in preventing deaths.

HMNews: Are there any treatment options in sight, such as antiviral drugs that can block entry into host cells or stop virus replication?

Abraham: One of the main causes of damage from the EEE virus involves two cellular receptors: the very low density lipoprotein receptor (VLDLR) and the apolipoprotein E receptor 2 (ApoER2). Several labs, including ours, are studying the use of a decoy molecule that mimics the receptor to lure the virus away, bind to it, and prevent it from entering human neurons.

But developing treatments is just as challenging. It's about identifying infected people quickly so they can be treated as soon as possible. Because some people get a fever and quickly fall into a coma, but by the time we do the test, the virus has generally already disappeared from the body. We need rapid diagnostic tests to identify and treat active viral infection early.

As for developing a vaccine, efforts to develop one have been hampered by the fact that EEE outbreaks are fairly sporadic, and it is difficult to predict who would benefit most from vaccination and when. However, there are some exciting advances in vaccine development against the EEE virus.

HMNews: The last fatal outbreak of Eastern Equine Encephalomyelitis in humans occurred in 2019. Do we know what is causing this up and down?

Abraham: No, that's not true. It's most likely related to ecological factors. For example, when it rains more, there are more mosquitoes and therefore more opportunities for transmission. But we're certainly missing pieces of the puzzle. One of those pieces is immunity. It probably fluctuates. It could be that in the five years since 2019, human immunity has slowly waned and we're now feeling the consequences.

The virus's life cycle is from birds to mosquitoes and back to birds. Humans and horses are dead-end hosts because the virus does not replicate in high enough concentrations in the blood to provide a good route of transmission to feeding mosquitoes. But the virus can kill these dead-end hosts.

Another important question is what happens to immunity and infection rates in birds over time.

HMNews: How do you think the current outbreak will unfold?

Abraham: The 2019 outbreak occurred in several states and included 38 cases, making it the largest outbreak in 50 years. Then the weather got cold, it got windy, and then COVID came.

This latest outbreak should remind us that this is not our first bout with the EEE virus, nor will it be our last. It is a reminder that we should have humility and respect towards these viruses. As we have learned from COVID, viruses are unpredictable.

What happens next is uncertain, but we need to remain vigilant about the possibility that this virus will mutate. We need to think about what happens if it figures out how to infect people in a way that allows it to spread from person to person. Of course, that would be a serious problem even if the virus lost some of its ability to cause severe disease, as many viruses do when they evolve toward greater transmissibility.

HMNews: As an infectious disease clinician and researcher studying the EEE virus, what precautions do you take?

Abraham: I try everything I can to reduce the risk of mosquito infection, such as wearing protective clothing and following the recommendations of local health authorities, including curfews, because although severe infection is unlikely in individual cases, it can have truly devastating consequences.

This interview has been edited for length and clarity.