Genomic characterization of highly pathogenic avian influenza A H5N1 virus newly emerged in dairy cattle

Abstract

In March 2024, the emergence of highly pathogenic avian influenza (HPAI) A (H5N1) infections in dairy cattle was detected in the United Sates for the first time. We genetically characterize HPAI viruses from dairy cattle showing an abrupt drop in milk production, as well as from two cats, six wild birds, and one skunk. They share nearly identical genome sequences, forming a new genotype B3.13 within the 2.3.4.4b clade. B3.13 viruses underwent two reassortment events since 2023 and exhibit critical mutations in HA, M1, and NS genes but lack critical mutations in PB2 and PB1 genes, which enhance virulence or adaptation to mammals. The PB2 E627 K mutation in a human case associated with cattle underscores the potential for rapid evolution post infection, highlighting the need for continued surveillance to monitor public health threats.

Keywords: H5N1; Highly pathogenic avian influenza (HPAI); clade 2.3.4.4b; dairy cattle; genome sequence; reassortment events.

Figure 1.

MCC tree of the HA genes of clade 2.3.4.4b H5N1 viruses in the United States since 2021. The MCC tree is constructed by using BEAST v1.10.4 software package. Each branch is coloured using posterior probability. The red frame represents H5N1 of Texas in 2024. The H5N1 viruses isolated in this study are shown in red, human isolate is shown in blue.

Figure 2.

Schematic representation of genomic composition and reassortment time of HPAI H5N1 viruses from dairy cattle and other animals and human in March 2024. Viral particles are represented by coloured ovals containing horizontal bars representing the eight gene segments (from top to bottom: PB2, PB1, PA, HA, NP, NA, M, and NS). Each colour represents a separate virus background. The illustration is based on GenoFLU (https://github.com/USDA-VS/GenoFLU) and phylogenetic analysis. ML: mallard, RT: ruddy turnstone, AB: Alberta, DB: Delaware Bay.