USA researchers uncover genetic clue that could help stop foot-and-mouth disease

USA – Researchers from the University of Connecticut and the U.S. Department of Agriculture have identified a promising genetic target that could help contain and control foot-and-mouth disease virus (FMDV), a highly contagious pathogen that poses a serious threat to livestock industries globally.

Although FMD has been eradicated from the United States since 1929, experts warn that the risk of reintroduction remains high due to the virus’s rapid spread and continued presence in many parts of the world. 

“This is critical because FMD is one of the fastest-replicating and spreading viruses known to man,” said Steven Szczepanek, associate professor in UConn’s Department of Pathobiology and Veterinary Science. “By the time you detect the virus on one farm, it’s likely already moved to adjacent farms, so it’s extremely challenging to control.”

The findings, recently published in the Journal of Virology, highlight the role of a gene called myeloid cell leukemia 1 (MCL 1) in significantly reducing FMDV replication. The discovery opens new avenues for developing targeted therapies or preventive tools that could provide an alternative to economically devastating measures like mass culling.

New tools to fight an age-old threat

Spearheaded by Szczepanek, graduate student Aishwarya Mogulothu, and USDA researchers Teresa de los Santos and Gisselle Medina, the study was born from a summer fellowship project through the Oak Ridge Institute for Science and Education (ORISE). 

Mogulothu conducted her research at a USDA high-containment facility, a necessity for working with the reportable FMD virus.

The research leveraged a unique library of cell lines engineered to overexpress specific interferon-stimulated genes (ISGs), which are part of the cell’s natural antiviral defences. 

By tagging the virus with fluorescent markers, the team could visually measure how well each ISG suppressed viral replication. 

“FMDV replicates super quickly, so we see a very bright signal,” Szczepanek explained. “Whereas if an ISG has an effect on the virus, we see the signal dim.”

Among the hundreds of genes screened, several showed potential, but MCL 1 stood out for its strong suppressive effect, despite having no previous link to viral defence. 

“Nobody has ever published anything on this gene in relation to FMD. In fact, it’s not even well characterised as an antiviral gene,” said Szczepanek. “It was characterised in the cancer space, so there are a lot of functions associated with MCL 1 that are known.”

Mitochondrial protection may hold the key

Further investigation revealed that MCL 1’s protective effect may stem from its role in maintaining mitochondrial health. The researchers discovered that FMDV appears to disrupt mitochondrial function as a way to disarm the cell’s defences. 

However, MCL 1 overexpression was found to shield mitochondria from these effects. “That was an exciting finding,” said Szczepanek.

The project faced delays due to COVID-19 and technical setbacks, but the team persisted. “There were a whole bunch of things we started with that did not have an effect,” Szczepanek said. “It was discouraging during the early days… it turns out, of course, the last couple of things we tried had an effect.”

Szczepanek emphasised that such foundational research is vital for informing long-term disease preparedness strategies. 

“Basic science is critical because it informs therapeutic strategies later on,” he said. “We need to understand the full scope of how biological systems function, so somebody can look at that information to develop new treatments.”

With the U.S. beef and pork industries valued at hundreds of billions of dollars, the stakes of an FMD outbreak are enormous, not just for animal health but for trade, food security, and the economy. 

“Many countries have trade restrictions with any country that is FMD positive,” said Szczepanek. “So the United States goes to great lengths to ensure that we maintain our FMD-free status.”

Now, with MCL 1 on the radar, researchers are hopeful this discovery will lead to more targeted and effective tools to safeguard livestock, reduce economic risks, and eliminate the need for blunt control methods such as culling.

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