A research team led by Associate Professor Steven Szczepanek from the Department of Pathobiology and Veterinary Science at the University of Connecticut has published groundbreaking research in the Journal of Virology, revealing a potential gene target for inhibiting the replication of Foot-and-Mouth Disease Virus (FMDV). This provides a scientific basis for developing new prevention and control technologies. The study was funded by the U.S. Department of Agriculture and key experiments were conducted in high-containment laboratories.
Although the United States eradicated foot-and-mouth disease in 1929 through large-scale culling and strict quarantine measures, the disease remains endemic in more than 60 countries worldwide. Szczepanek warned that FMDV is one of the fastest-spreading animal viruses known, capable of spreading across farms within 24 hours. Once an outbreak occurs, it would trigger global trade bans and directly impact the U.S. meat industry, which is worth hundreds of billions of dollars.
Current control relies on a "detect-and-cull" strategy, but vaccination may trigger a market confidence crisis. "Proactive vaccination would be seen as admitting risk, causing meat prices to drop by 15%-20%," Szczepanek noted. This "disease-free but seemingly diseased" market perception forces the United States to continue investing heavily to maintain its disease-free status.
The research team constructed a cell library containing hundreds of interferon-stimulated genes (ISGs) and used fluorescent labeling technology to screen for genes that significantly inhibit FMDV replication. Among them, the MCL-1 gene — previously well-known in cancer research — stood out prominently:
Mitochondrial Protection Mechanism: FMDV destroys mitochondrial function to evade immunity, while overexpression of MCL-1 can maintain mitochondrial integrity.
Replication Blocking Effect: Experiments showed that MCL-1 activation can reduce the intensity of viral fluorescent signals by more than 70%.
New Mechanism of Action: This gene had not previously been reported to have antiviral functions, and its mechanism is completely different from existing drug targets.
The study was completed in BSL-3+ laboratories such as the Plum Island Animal Disease Center. Team member Dr. Aishwarya Mogulothu participated through the ORISE fellowship program. She described the experimental challenges: "The virus replicates much faster than imagined. Many early attempts failed, and we ultimately discovered that the virus spreads by hijacking the cell's autophagy mechanism."
Although the COVID-19 pandemic caused an 18-month interruption in the research, the team persisted and completed all validations. Szczepanek emphasized the importance of basic science: "We must first understand the interaction network between the virus and host cells before we can develop precise intervention methods. This discovery opens a new path for designing broad-spectrum antiviral drugs."
The U.S. Department of Agriculture has launched a special program to incorporate MCL-1 research into the framework for developing next-generation vaccines. At the same time, the scientific community is calling for the establishment of a dual-track mechanism of "routine prevention and emergency response during outbreaks," using gene editing technology to breed disease-resistant varieties and combining it with intelligent monitoring systems for early warning.
Background Information
Foot-and-mouth disease causes global agricultural losses of more than $12 billion annually. The 2001 outbreak in the United Kingdom led to the culling of 10 million head of livestock. China has been building FMD-free zones since 2011, and six provinces have already received OIE certification. This latest discovery provides a U.S. solution for global foot-and-mouth disease control, and the related patents have entered the application stage.
