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In a critical review published in the journal Nature, researchers highlight alarming developments concerning the H5N1 high-pathogenicity avian influenza (HPAI) virus, which is mutating rapidly and adapting to mammalian hosts. This raises significant concerns about its potential to trigger the next pandemic.
Background
Influenza A viruses are notorious for being behind numerous global pandemics. H5N1, a subtype of avian influenza, has long been considered a major risk factor for future outbreaks. Recent findings suggest that the evolutionary barriers preventing these viruses from adapting to mammals are lower than previously believed. This is evidenced by a rapid accumulation of mutations in key viral proteins.
Historically, H5N1 viruses were predominantly detected in Asian poultry over the past two decades. However, a troubling trend has emerged, as these viruses have begun to infect a wider range of mammal species across the globe, threatening wildlife, agriculture, and human health. The surge in cases can be traced back to a new genotype of H5N1, known as clade 2.3.4.4b, which has been identified in migratory birds from Europe to South America and even Antarctica.
Genomic Reassortment and Adaptation
The emergence of this new genotype is attributed to genomic reassortment involving H5N8 and low-pathogenicity avian influenza (LPAI) viruses. This genetic mixing has led to the creation of hybrid strains capable of adapting swiftly to new environments.
The rapid transmission of the panzootic 2.3.4.4b H5N1 viruses can occur covertly, as migratory aquatic birds carry the virus to new regions. This poses risks of mass die-offs in bird populations and could affect predators that consume infected birds, potentially leading to neurological disorders.
Key adaptive mutations have been observed in the polymerase (PB2) and hemagglutinin (HA) genes, enhancing the virus’s ability to replicate in mammalian hosts. This raises urgent concerns regarding the virus’s capacity for mammal-to-mammal transmission.
Case Studies of Concern
The review discusses three significant case studies illustrating the increasing risk of H5N1 transmission among mammals:
- European Fur Farms: Recent outbreaks on fur farms have revealed the presence of mammalian-adaptive mutations in the PB2 gene, particularly the PB2 E627K mutation, known to enhance viral replication in mammals. Investigations indicate that farm-to-farm transmission likely occurred through contaminated equipment or infected carcasses.
- South American Marine Mammals: A new reassortant H5N1 genotype arrived in South America in late 2022, leading to mass die-offs among coastal birds and marine mammals. Genetic analysis confirmed the presence of adaptations that facilitate mammalian transmission, with the virus spreading from infected marine mammals to humans.
- US Dairy Cattle Outbreaks: In 2024, Texas dairy cattle outbreaks linked to the B3.13 genotype underscored the potential for H5N1 viruses to adapt within mammalian populations. Phylogenetic analysis indicated a single introduction from wild birds, with adaptations allowing the virus to replicate efficiently in cattle.
Implications for Public Health
While fewer than 20 human cases of 2.3.4.4b H5N1 viruses have been reported in Europe and the US since 2020, the low fatality rates observed in recent human infections contrast sharply with the higher rates recorded during earlier outbreaks in Asia.
The potential for H5N1 to continue spreading among humans poses a significant threat. Should this occur, existing H5 vaccines, which are antigenically related to the circulating strains, could be rapidly adapted using mRNA technology. However, the virus’s ability to reassort with other influenza strains, especially in high-risk environments such as farms, raises concerns about the emergence of more transmissible variants.
As the world grapples with the ongoing challenges posed by zoonotic diseases, the findings from this review underscore the urgent need for surveillance and preparedness strategies to mitigate the risk of a future pandemic.
For further reading, the full study can be accessed here: Peacock, T., et al. (2024). The global H5N1 influenza panzootic in mammals. Nature. DOI:10.1038/s41586-024-08054-z.
