Infectious Diseases 2024

Two report parts on the genomic epidemiology of the 2024 H5N1 influenza A virus outbreak in U.S. cattle were published on virological.org by more than 20 researchers. Here, we summarize the main conclusions. A reassortment event within North American avian H5N1 2.3.4.4b viruses occurred shortly before the start of the cattle outbreak. The cattle sequences are all Genotype B3.13. This genotype is a reassortant between the Eurasian panzootic H5N1 genotype and low pathogenicity North American genotypes first seen in late 2023. The PA, HA, NA and MP are derived from the European genotype and PB2, PB1, NP and NS derived from North American genotypes. This genotype is relatively rare in the USA but has been seen in birds as well as in wild mammals. Genotype B3.13 differs from the virus seen in a recent outbreak where H5N1 2.3.4.4b influenza A virus spilled over from poultry to goats. The outbreak in goats was unrelated to the current cattle outbreak.
The cattle outbreak likely had a single origin from the avian H5N1 reservoir. The viruses sampled from cattle form a monophyletic clade in each segment, consistent with a single introduction of H5N1 into cows and indicative of cattle-to-cattle spread.
The H5N1 outbreak in cattle likely went undetected and unidentified for an extended period and is now several months old. The researchers estimated the median time of this most recent common ancestor (tMRCA) of the cattle clade and avian H5N1 as 13 November 2023 (95% HPD: [25 Sep 2023, 3 Jan 2024]). Hence, the jump from the avian reservoir into cattle likely happened between ~13 November 2023 and ~18 January 2024.
The original cattle H5N1 virus’s HA was not adapted to a human-like receptor. In the hemagglutinin (HA), the protein that must bind to the host’s cell-surface sialic acid residues for the virus to gain entry to the host cell, the closest-related sequences to the cattle H5N1 HAs come from wild birds (a Canada goose and a peregrine falcon.) There are no amino acid differences between the HAs of these wild bird sequences and the earliest sequences from cattle.
This suggests that the first cattle sequences possessed no (pre)adaptation to mammalian cell-surface receptors. Without changes in HA affecting receptor binding, the risk of the virus becoming transmissible between humans is low.
A virus closely related to, but distinct from, those sampled from cattle was sampled from an individual who was reportedly a dairy farm worker. The human sequence (A/Texas/37/2024) does not share multiple substitutions present in all the cattle sequences.
 

Schematic depicting the phylogenetic relationships between the HA segment of the viral genomes in different host species and when H5N1 likely spilled over into cattle (source: virological.com)