A single mutation in avian influenza in cows could enable human-to-human transmission
The authors of a study published in ‘Science’ emphasize the importance of monitoring mutations in both avian and bovine strains of the virus to prevent a potential future pandemic
When early humans domesticated animals and began living alongside them, they could not have foreseen that, in addition to providing meat and skins, these animals would also bring devastating epidemics. Coexistence with animals facilitated the transmission of pathogens between species, and the cities that flourished due to agriculture and livestock were periodically decimated by outbreaks. These epidemics changed the course of history. The Cyprian plague of the third century spurred the rise of Christianity, the Justinian plague weakened the empires of the Near East and contributed to the rapid expansion of Islam, and the Mexican empire fell to a small group of Spaniards who were immune to smallpox.
As the global population has surged in the last century, the frequency of outbreaks has increased. A paper published in Science on Thursday warns that a single mutation in the H5N1 avian flu virus, which currently infects cows, could alter its affinity from animal cells to human cells. Although human-to-human transmission has not yet been reported, the virus has already been detected in at least 282 dairy herds in the U.S. The study suggests that a small change in the hemagglutinin (the “H” in H5N1) could mark the beginning of a more dangerous situation.
The influenza virus infects its host by attaching to cell receptors via hemagglutinin. This protein normally binds to receptors on bird cells, but not typically on human cells. However, viruses have spread globally on migratory birds, jumping between animals, and sometimes mutating to infect new hosts. This occurred when the H5N1 avian influenza, first identified in 1996, reached cows, becoming a bovine disease. In January 2024, the first known case of a human infected with “cow flu” was reported in Texas.
Until now, it was thought that at least three mutations were required for a bird flu virus to infect humans and spread between them. However, in the Texas case, a single mutation in an amino acid of the hemagglutinin allowed the virus to bind to human cell receptors.
Researchers at Scripps Research in San Diego tested the virus in the lab, introducing mutations that could occur naturally. One mutation, Q226L, enhanced the virus’s ability to infect human cells, particularly in the respiratory tract. “This discovery demonstrates how easily the virus can evolve to recognize human receptors,” says Ting-Hui Lin, co-author of the study. However, Lin adds a reassuring note: “Our study does not suggest that this evolution has happened, nor that the current H5N1 virus would be transmissible between humans with this mutation alone.”
Rafael Toledo, a professor of Parasitology at the University of Valencia in Spain, agrees that the mutation marks only the first step in the virus’s potential to infect humans. “This mutation might have other effects on the virus’s biology that, overall, could make it less effective,” he explains. “Or while the virus may access human cells, it might not be able to replicate afterward.”
Toledo continues: “The problem is not so much that the virus reaches humans, but that it multiplies and is transmitted effectively. This involves many parameters that are not included in this study.” Nonetheless, he considers the research crucial for understanding the virus, aiding in epidemiological surveillance, and preparing vaccines or treatments in case of a pandemic.
Pandemic viruses often thrive in environments where multiple species of animals interact, facilitating the exchange of genetic material. Random mutations can create the ideal conditions for a virus to spread among humans. Angela Vázquez, a researcher at the Severo Ochoa Molecular Biology Center of Spain’s CSIC research center, highlights a noteworthy finding from the study: “The udders and respiratory tracts of cows have the typical receptors found in both birds and humans.” This dual receptor presence could allow cows to act as a mixing vessel, where viral strains from different species combine and mutate, potentially creating a more dangerous form of the virus.
The authors of the Science paper acknowledge the limitations of their study and the complexities of real-world infections. However, they emphasize that the growing number of H5N1 cases in humans with direct animal contact necessitates close monitoring of the virus’s evolution. As history has shown, such changes can lead to dramatic consequences.
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