Seventeen months ago, a notable outbreak of highly pathogenic H5N1 avian influenza was identified in dairy cattle located in Nebraska, USA. The virus not only spread among the cattle but also returned to infect poultry, wild birds, other mammals, and even humans.
In a recent article published in Nature Communications, a team of researchers from The Pirbright Institute and its six collaborating organizations have explored how this virus has rapidly adapted to cattle while concurrently enhancing its ability to replicate in mammalian cells, including those of humans.
The investigation focused on the B3.13 genotype of H5N1 circulating within US dairy herds. Researchers discovered that the virus swiftly accumulated specific mutations in its polymerase genes, which are crucial for viral replication as it transitions from birds to mammals.
Virus Interaction with Mammalian Cells
Through a combination of genetic, structural, and functional analyses, the research unveiled that the mutation PB2 M631L significantly improves the viral polymerase’s interaction with a vital host protein known as ANP32—specifically the bovine variant, ANP32A. This interaction is fundamental for effective viral genome replication, allowing mutant viruses to replicate more proficiently in bovine mammary tissue, respiratory cells, and primary human airway cultures.
Ongoing evolution of the virus was evident in cattle, with additional polymerase mutations such as PB2 E627K and the commonly emerging PB2 D740N shown to boost viral replication across various mammalian cells without negatively impacting its replication in birds.
Concerns Over Viral Adaptation
Dr. Thomas Peacock, a co-corresponding author and Fellow at The Pirbright Institute, stated, “Our findings indicate that the circulation of H5N1 in dairy cattle is actively promoting its adaptation to mammalian species. This adaptation enhances the virus’s replication capability in cattle and raises the concerns regarding zoonotic spillover.”
Dr. Peacock further elaborated that, while current evidence suggests limited human transmission, the continuous exposure and viral evolution increase the potential for further adaptations that might enhance transmissibility among humans.
Call for Surveillance and Vaccine Development
The study emphasizes the necessity of continuous surveillance of influenza viruses within cattle and other animal populations, with a particular focus on monitoring changes in polymerase genes that might signify adaptation to mammals. The researchers have urged for the swift development of broadly protective H5 influenza vaccines applicable to both animals and humans.
This study involved contributions from scientists affiliated with the Royal Veterinary College, Imperial College London, The Roslin Institute, Great Ormond Street UCL Institute of Child Health, MRC University of Glasgow Centre for Virus Research, and the University of Oxford.
The full paper titled Polymerase mutations underlie early adaptation of H5N1 influenza virus to dairy cattle and other mammals is now accessible.
