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Study: Mutations in Everglades virus portend possible new threat to large mammals

By Sarah Carey

In a new study, University of Florida researchers report that Everglades virus, or EVEV — endemic in South Florida and a subtype of the highly pathogenic Venezuelan equine encephalitis — has mutated, suggesting a possible new threat to horses and other large mammals.

Dr. Maureen Long

“This virus is changing and it’s changing in the protein that binds to cells. This is important because it may change what mosquitoes can transmit the virus and what hosts it can infect,” said Maureen Long, D.V.M., Ph.D., a professor of virology and equine medicine at the UF College of Veterinary Medicine. “While we don’t know the meaning of this particular change without further study, in mosquito-borne viruses, it only takes one or two mutations to have profound effects on human and animal disease.”

A recent example of this occurred with another closely related mosquito-borne virus, Chikungunya, which causes debilitating and infectious arthritis. This virus caused disease sporadically in humans for many years before mutating once or twice to jump into a new, more widespread mosquito, leading to worldwide outbreaks.

A map of southern Florida showing locations of EVEV samples from public lands. Circles indicate the current study, and diamonds indicate previous studies.

The EVEV study, published recently in Virus Evolution, was coauthored by Long, Carla Mavian, M.D., Ph.D., an assistant scientist who studies the molecular evolution of infectious diseases in the UF College of Medicine and others, including Monica Valente, a D.V.M. student who participated in the Florida Veterinary Scholars Program, and graduate student Dhani Prakoso, who performed the sequencing of the virus itself. This project was funded by the UF Research Opportunity Seed Grant and involved the combined efforts of Jason Burkett-Cadena of the UF-IFAS Florida Medical Entomology Laboratory, Robert McCleery of the department of wildlife ecology and conservation and Long at the College of Veterinary Medicine.

Researchers say this is the first report that shows in detail the evolution of EVEV in South Florida.

First isolated in the 1960s, antibodies to EVEV were discovered in humans, along with mostly rodents and some dogs, Long said. The virus was also reported to cause febrile illness in a human. Prior to this current work only two isolated viruses had been sequenced — one from the 1960s and the other from 2013, she added.

“Importantly, this virus is in the same family as Venezuelan equine encephalitis, or VEEV, which was eradicated from the United States but is always a constant threat. The VEEV virus can cause severe epidemics as well as infections in horses such that the horse can transmit the virus,” Long said. “The Everglades virus, which has been hanging around in mosquitoes and cotton rats in the swamps of that region, has had a very narrowly defined life cycle with the mosquito that transmits it. People and animals might get exposed but probably don’t get severe disease.”

But two new recent mutations, which researchers pinpointed through gene sequencing and phylogenic analysis, showed that isolates of the virus had clustered, based on the location of sampling, into two monophyletic clades that diverged in 2009. These new mutations may result in adaptation to a mosquito vector or new host, the paper states.

“Finding these recent mutations could be fairly meaningful for understanding the future activity of EVEV and whether or not this virus has the capacity to cause more disease in humans and horses and other species, as happens with VEEV,” Long said.

The evolutionary aspect of the virus is worth noting: how and why the virus has changed over time, and what those changes portend for human and animal health, she added.

“We can look at these phylogenies, or clusters, of the isolates and build a time clock,” Long said. “We see very specific times where we see these mutations have occurred since the 1960s, and they’re probably associated with climatic events, such as hurricanes and changes in water.

“In addition, in work performed and published as part of the larger project, we’re seeing cotton rats in the region much more highly infected now. This may end up causing a larger chance for mutation because the rats are one of those species in which the virus replicates to high levels. The more you replicate a virus, the greater the chance for mutation,” she said.

“This zoonotic pathogen warrants inclusion into routine surveillance, given the high natural infection rate in the host as well as the ongoing mutations in this particular protein of the virus,” the authors state in the paper. “Invasive species, increasing urbanization, the Everglades restoration and modifications to the ecosystem due to climate change and habitat fragmentation in South Florida may increase rates of EVEV spillover to the human population.”