U.S. NIH Finds American Bovine H5N1 Shows Enhanced Neurotropism Compared to Lethal Vietnamese Human H5N1 Strain
Nikhil Prasad Fact checked by:Thailand Medical News Team May 24, 2025 1 day, 12 hours, 33 minutes ago
Medical News: A Worrying Mutation in the Bird Flu Virus Shows Dangerous Behavior in the Brain
In a major new development raising concerns over a potential pandemic threat, scientists from the National Institute of Allergy and Infectious Diseases (NIAID) at the U.S. National Institutes of Health have uncovered alarming evidence that a bovine version of the H5N1 avian influenza virus found in the United States displays a far stronger ability to attack brain tissue than a known human strain. In a controlled laboratory study, researchers found that the bovine H5N1 virus strain, isolated from infected dairy cattle in Ohio in 2024, replicated widely throughout the brains of mice and led to clear signs of neurological illness.
U.S. NIH Finds American Bovine H5N1 Shows Enhanced Neurotropism Compared to Lethal Vietnamese Human H5N1 Strain
By contrast, a well-studied human H5N1 virus strain from a fatal case in Vietnam in 2004 showed far less ability to invade the central nervous system (CNS), with most of its activity limited to the respiratory system. This
Medical News report explores how these findings suggest that some newly emerging strains of H5N1 may pose higher risks to mammals — and potentially humans — than previously thought.
A Head-to-Head Comparison of Two Dangerous Viruses
To evaluate how the two strains differ, researchers exposed C57BL/6J mice to each virus through aerosolized particles — mimicking natural airborne infection. While both strains proved uniformly lethal at higher doses, there were striking differences in what organs the viruses preferred. The Vietnamese H5N1 strain mainly infected the lungs, while the bovine strain, dubbed Bov342, not only targeted the lungs but spread aggressively into multiple regions of the brain.
Animals infected with Bov342 developed tremors, loss of balance, and other neurological symptoms not observed in mice infected with the older VN1203 strain. Immunohistochemistry and molecular testing revealed high viral loads in the brain, especially in the olfactory bulb, cerebral cortex, and cerebellum. Intriguingly, Bov342 was also found replicating in the retina, dental pulp, inner ear, and choroid plexus — tissues where influenza viruses are rarely detected.
A Storm of Inflammation in the Brain
Further investigation showed that Bov342 triggered a powerful immune reaction in the brain, with elevated levels of interferons and inflammatory cytokines like IL-6, TNF-alpha, and IL-1β. These chemicals, part of the body’s defense system, can also cause damage when uncontrolled. This intense immune response was absent in the mice infected with the VN1203 strain, even at similar viral doses.
The study also revealed a dose-dependent effect — higher exposure levels to Bov342 led to more severe brain inflammation and quicker onset of symptoms. In the lungs, both virus strains caused similar levels of tissue damage, but the differences in brain infection were dramatic.
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t;strong>Genetic Clues Behind the Neurotropism
Scientists believe the increased neurotropism of Bov342 could be linked to genetic mutations in the virus. While VN1203 contains the well-known PB2 E627K mutation that enhances replication in mammals, Bov342 lacks this change. However, it carries a different mutation, PB2 M631L, which may also improve the virus's ability to replicate in human-like cells. Another rare mutation, PB2 R251G, was found in the brains of Bov342-infected mice and could be contributing to its unique behavior.
Interestingly, although other animal models like ferrets and BALB/c mice have shown varying results in terms of brain infection, this study underlines how different mouse strains or exposure methods (aerosol vs. nasal drops) can influence how the virus spreads in the body.
Implications for Humans and the Need for Urgent Research
To date, most human cases of H5N1 — including those from recent bovine-linked infections in the United States — have been mild, typically involving eye or respiratory symptoms. However, the discovery that a bovine strain of H5N1 can invade the brain in mice raises serious questions. Could similar behavior occur in humans under certain conditions? And if so, what long-term effects might result from viral invasion of the brain?
The researchers urge that more studies are needed to investigate the mechanisms behind this shift in viral behavior and to monitor new mutations closely. The findings also emphasize the importance of using animal models to evaluate the potential neurotropism of emerging strains and to develop targeted treatments or vaccines.
Conclusion
This groundbreaking study shows that while both the human and bovine versions of the H5N1 virus are lethal in mice, the newer bovine strain demonstrates a disturbing ability to infect the brain, unlike its human counterpart. This increased neurotropism could make it more dangerous if it adapts to human hosts. The immune system's response in the brain and the unusual spread of the virus to eye and dental tissues are concerning and warrant further investigation. Although these results were observed in mice, they underscore the need for vigilant surveillance and advanced research to prepare for any possible future outbreak.
The study findings were published in the peer reviewed journal: npj Viruses
https://www.nature.com/articles/s44298-025-00121-0
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