Research supported by the National Institutes of Health suggests that a lone alteration in the protein on the exterior of the highly pathogenic H5N1 avian influenza strain, which is now present in US dairy cattle, may enhance its transmission to humans. The findings, now published in Science, emphasize the critical necessity for ongoing, diligent observation of H5N1’s genetic mutations that might elevate human transmission risks.
Currently, the bovine variant of the H5N1 virus isn’t deemed transmissible among humans. However, infections have happened in individuals exposed to infected wild birds, poultry, dairy cattle, and other animals. As part of pandemic readiness activities, scientists have been closely monitoring the H5N1 virus for decades to grasp the genetic changes occurring in nature and their potential impact on viral transmission.
Flu viruses attach to cells using a surface protein known as haemagglutinin (HA), which binds to sugar (glycan) receptors on cells to initiate infection. Avian influenza viruses, such as H5N1, seldom infect humans since the human upper respiratory system lacks the avian-type cell receptors. Nevertheless, there is scientific concern that the virus might evolve to identify human-type receptors, thereby gaining the capability to infect and spread among humans.
Using the H5N1 strain isolated from the first US bovine strain-related human infection, identified as 2.3.4.4b (A/Texas/37/2024), researchers at Scripps Research evaluated how mutations in the HA gene influenced its interaction with avian versus human-like receptors. They introduced various mutations previously observed in nature into the viral HA protein, discovering that one, termed Q226L, notably improved protein affinity for human cell receptors, particularly when combined with another mutation. Crucially, the scientists only mutated the HA surface protein, refraining from creating or testing a fully infectious virus.
The presence of the Q226L mutation does not imply that HPAI H5N1 is on the brink of a global epidemic, the study’s authors clarify. Likely, additional genetic alterations would be necessary for the virus to spread among humans. With the growing number of human H5N1 cases linked to direct contact with infected animals, these findings underscore the significance of continuous outbreak management and genomic oversight to track potential genetic shifts in HPAI H5N1 and support public health measures.
The study received partial funding from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), under its Centers of Excellence for Influenza Research and Response program.
NIAID leads and funds extensive research projects at NIH, nationwide, and worldwide, focusing on infectious and immune-mediated disorders, aiming to enhance prevention, diagnostics, and treatments.
The National Institutes of Health, the cornerstone of medical research in the US, consists of 27 Institutes and Centers under the US Department of Health and Human Services umbrella. NIH primarily conducts research into common and rare diseases, seeking treatment and cure solutions.