Genomic epidemiology of the H5N1 outbreak in US cattle


Trevor Bedford

Fred Hutchinson Cancer Center / Howard Hughes Medical Institute
14 May 2024
Monthly Meeting
Northwest PGCoE
Slides at:

Confirmed infections in cattle in nine states with first detection on March 25

Genomic analysis

with Louise Moncla, James Hadfield and John Huddleston

Broader context of H5N1 evolution and spread

Introduction into Europe and the Americas of clade

Spread in the Americas characterized by spillover to multiple mammalian hosts

Cattle infections form distinct clade across segments indicative of single spillover and cow-to-cow spread

HA, PB2, PA,

Reassortment in birds prior to cattle spillover, but cattle clade appears non-reassorting

Full genome analysis of concatenated segments provides substantially finer resolution

Growing epizootic in cattle after introduction in ~Dec with subsequent spillback into birds

Molecular clock dating introduction into cattle

Human case outgroups to cattle infections, suggesting unsampled diversity and potentially a second cattle introduction

Epizootic origin appears to be Texas congruent with initial cases

But note sampling bias, where 119 of 189 cattle-derived sequences were sampled from Texas

Specific amino acid changes associated with cattle adaptation

Data systems

Timeline of initial genomic data

Mar 25
First confirmed detection in Texas, with 10 farms in three states on Mar 30
Mar 27
Six viral genomes from Texas shared to GISAID by NVSL and a seventh on Apr 5
Apr 21
Raw reads for 239 samples shared to SRA (but lack metadata)
Apr 22
Karthik Gangavarapu assembles these reads and shares consensus genomes to GitHub
Apr 26
Florence Débarre shares metadata scraped from USDA YouTube presentation
May 1
Nguyen et al preprint shared to bioRxiv
May 2
Consensus genomes and metadata for 170 samples from Nguyen et al shared to GISAID by NVSL
May 3
Consensus genomes and metadata for Nguyen et al samples shared to GenBank

Current genomic data

Filtered to just cattle sequences

177 consensus genomes with metadata (from Nguyen et al)
176 consensus genomes with metadata available via this NCBI Virus query (from Nguyen et al)
211 samples without metadata available via this SRA Run Selector query

Sequences from cattle and other hosts

Currently 460 samples in BioProject PRJNA1102327 with 322 propagated to SRA Run Selector

Current Nextstrain dataflow

Prospective Nextstrain dataflow

Scientific questions addressable by genomic epi

  • Is the epizootic rate of growth slowing?
  • Are movement restrictions working to keep geographic spread contained?
  • Is adaptive evolution to novel cattle host continuing?


H5N1 genomic data: APHIS National Veterinary Services lab at the USDA for sharing cattle sequences, other data producers from all over the world for sharing contextual sequences, GISAID for collating data and Karthik Gangavarapu and colleagues for sharing assembled consensus genomes

H5N1 genomic analysis: Louise Moncla, James Hadfield, John Huddleston

Nextstrain: Richard Neher, Ivan Aksamentov, John Anderson, Kim Andrews, Jennifer Chang, James Hadfield, Emma Hodcroft, John Huddleston, Jover Lee, Victor Lin, Cornelius Roemer, Thomas Sibley

Bedford Lab: John Huddleston, James Hadfield, Katie Kistler, Thomas Sibley, Jover Lee, Miguel Paredes, Marlin Figgins, Victor Lin, Jennifer Chang, Eslam Abousamra, Nashwa Ahmed, Cécile Tran Kiem, Kim Andrews, Cristian Ovaduic, Philippa Steinberg, Jacob Dodds, John SJ Anderson