Highly pathogenic H5N1 avian influenza viruses (HPAIV) belonging to lineage 2.3.4.4b emerged in Chile in December 2022, leading to mass mortality events in wild birds, poultry, and marine mammals and one human case. We detected HPAIV in 7,33% (714/9745) of cases between December 2022–April 2023 and sequenced 177 H5N1 virus genomes from poultry, marine mammals, a human, and wild birds spanning >3800 km of Chilean coastline. Chilean viruses were closely related to Peru’s H5N1 outbreak, consistent with north-to-south spread down the Pacific coastline. One human virus and nine marine mammal viruses in Chile had the rare PB2 D701N mammalian-adaptation mutation and clustered phylogenetically despite being sampled 5 weeks and hundreds of kilometers apart. These viruses shared additional genetic signatures, including another mammalian PB2 adaptation (Q591K, n = 6), synonymous mutations, and minor variants. Several mutations were detected months later in sealions in the Atlantic coast, indicating that the pinniped outbreaks on the west and east coasts of South America are genetically linked. These data support sustained mammal-to-mammal transmission of HPAIV in marine mammals over thousands of kilometers of Chile’s Pacific coastline, which subsequently continued through the Atlantic coastline.
Key Points:
Genotype and Origin:
The H5N1 clade 2.3.4.4b viruses detected in Chile belong to the B3.2 genotype, characterized by a 4:4 reassortant genome.
These viruses retained four segments (PA, HA, NA, MP) from the Eurasian AIV lineage and acquired four new segments (PB2, PB1, NP, NS) from the American AIV lineage.
Phylogenetic analysis indicates a single introduction from North America into Peru and Chile, with the virus spreading north-to-south along the Pacific coastline.
Unprecedented Mammal-to-Mammal Transmission:
The H5N1 2.3.4.4b clade emerged in Chile in December 2022, leading to mass mortality in wild birds, poultry, marine mammals, and one human case.
The virus was detected in 7.33% of cases (714/9745) from December 2022 to April 2023.
Sequencing of 177 H5N1 virus genomes revealed that Chilean viruses were closely related to Peru's H5N1 outbreak, indicating a north-to-south spread along the Pacific coastline.
There is evidence of sustained mammal-to-mammal transmission of HPAIV in marine mammals over thousands of kilometers of Chile's Pacific coastline, continuing through the Atlantic coast.
Significant Increase in Marine Mammal Deaths:
An estimated 19-fold increase in historical marine mammal strandings and deaths has been observed since the first detection of H5N1 in Chile.
Most of the affected species included South American sea lions, marine otters, Burmeister’s porpoises, and Chilean dolphins.
Key Mutations Enabling Mammalian Transmission:
The virus exhibited mammalian-adaptation mutations in the PB2 gene, specifically D701N (in all marine mammal and the human virus) and Q591K (in 37 marine mammal viruses).
These mutations enhance viral replication and pathogenicity in mammals and are linked to the potential for mammal-to-mammal transmission.
Implications:
The double mutation (D701N/Q591K) and other unique mutations were not observed in wild birds, further supporting the idea of mammal-to-mammal transmission.
The virus's potential to evolve toward efficient human-to-human transmission raises concerns about a heightened risk of a global pandemic.
The unprecedented outbreak of H5N1 among marine mammals in South America may be linked to a suspected lab-derived strain originating from North America. Since May 2022, H5N1 clade 2.3.4.4b has been detected in over 40 mammalian species across the United States—an anomalous and sudden host-range expansion that raises serious concerns about potential laboratory manipulation. Our study, "Proximal Origin of Epidemic Highly Pathogenic Avian Influenza H5N1 Clade 2.3.4.4b and Spread by Migratory Waterfowl," underscores the need for rigorous investigation into the potential lab origins and spread of this highly adapted strain:
As highlighted in our study, since April 2021, serial passage gain-of-function experiments involving H5Nx clade 2.3.4.4b avian influenza have been underway at the USDA Southeast Poultry Research Laboratory (SEPRL). Notably, these experiments predate the unprecedented host range expansion of H5N1:
The virus continues to evolve as seen with the recent emergence of genotype D1.1:
Proactive measures are indicated to protect dairy and cattle frontline workers and minimize the risk of human infections, which could drive mutations that enhance the virus's adaptation to humans:
In a positive development, we received indication yesterday that USDA Secretary Brooke Rollins recognizes the serious risks associated with mass animal vaccination against H5N1 bird flu:
Not enough research had been done. We need to ensure it will actually help the problem, not make the virus stronger and jump to other species.
I'm not touching any of that all vexxxed up crap
Looks like we've caused a lot more problems than we thought we would solve.
Just stop messing around w bugs! Nature does a pretty good job- God IS the master of it, not man.