BREAKING! Three Novel HFMD Viral Hybrids Discovered in Beijing Raise Global Concern
Nikhil Prasad Fact checked by:Thailand Medical News Team May 12, 2025 5 hours, 3 minutes ago
Medical News: A major new study by Chinese researchers has uncovered alarming evidence that the virus responsible for hand, foot, and mouth disease (HFMD) is evolving into new hybrid forms, raising fresh concerns about global outbreaks. Scientists working in Beijing between 2019 and 2023 have identified three never-before-seen recombinant versions of Coxsackievirus A6 (CVA6)—the dominant virus currently causing HFMD in children across Asia.
Three Novel HFMD Viral Hybrids Discovered in Beijing Raise Global Concern
The study was led by experts from the School of Public Health at Xinxiang Medical University, the National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases at the Chinese Center for Disease Control and Prevention (China CDC), and the Institute for Infectious Disease and Endemic Disease Control at the Beijing Center for Disease Prevention and Control. Their work focused on 54 complete viral genomes obtained from pediatric HFMD patients in Beijing hospitals. This
Medical News report highlights how a specific mutation—T283A—has emerged as a genetic signature for a rapidly spreading new branch of CVA6 called “D3c.”
A New Evolutionary Wave of CVA6 in Asia
Nearly all of the 54 virus samples belonged to the D3c sub-genotype, which has now replaced earlier forms like D3a and D3b as the dominant strain in Beijing and other parts of China. This shift is not limited to China—D3c strains have also been identified in Japan, South Korea, Thailand, Vietnam, and even several countries in Europe and Oceania. The T283A mutation, found in 95.9% of D3c samples, alters a crucial protein on the virus’s surface, possibly allowing it to escape immune detection more effectively.
But even more troubling is the discovery of three completely new recombinant forms of the virus—named RF-Z, RF-AA, and RF-AB. These hybrids are the result of CVA6 exchanging genetic material with other enteroviruses like CVA2, CVA4, and CVA8. Such viral recombination can produce new strains with unknown behavior, infectivity, or severity.
Genetic Mixing Could Lead to New Health Threats
Researchers mapped out these recombination events by analyzing which parts of the viral genome had come from different “parent” viruses. RF-Z was found to share its genetic tail end with CVA2 and CVA4. RF-AA had parts similar to CVA8, while RF-AB contained segments matching CVA4. These mix-ups occurred in regions of the genome critical for virus replication and interaction with the human immune system.
Of particular interest was RF-AA, which appears to carry a unique genetic segment that did not match any known virus in public databases. This raises the possibility that the virus acquired genes from an unsampled or unknown strain. The hybrid variants also had more amino acid mutations in the recombined regions compared to the original virus, suggesting these changes could influence how easily the virus spreads or how dangerous it becomes.
Mutations in Key Immune Targets Detected
The study also found mutations in areas of the virus that serve as targets for neutralizing antibodies. These include the DE and HI loops of the VP1 capsid protein, which play an essential role in how the immune system recognizes and fights the virus. For instance, the RF-Z hybrid showed a rare S137D mutation in the DE loop, while RF-AA carried an S137N change in the same region, along with a V242I mutation in the HI loop. Another variant had a D138N mutation that directly affects a site known to bind human antibodies.
The recombined viruses displayed a higher number of amino acid mutations overall, especially in areas linked to immune evasion. Researchers believe this may help the virus spread more efficiently and possibly increase disease severity.
Conclusions and Global Implications
The discovery of three new hybrid forms of CVA6 in Beijing signals a worrying trend in viral evolution. These findings suggest that the virus is actively reshaping itself through recombination, possibly in response to growing immune pressure in the population. As CVA6 continues to mutate and mix with other enteroviruses, it may develop enhanced transmissibility, altered disease symptoms, or resistance to current vaccines and treatments.
Monitoring these genetic changes is critical. Health authorities should incorporate key mutations like VP1-T283A into surveillance systems and begin testing whether current neutralizing antibodies still work against these new variants. Developing updated vaccines and therapeutic strategies may also be necessary. The study further emphasizes the urgent need for international cooperation in virus monitoring, especially as human travel and population movement accelerate global spread.
The study findings were published in the peer reviewed journal: Virus Evolution.
https://academic.oup.com/ve/advance-article/doi/10.1093/ve/veaf036/8128483
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