OmniVira

Replication kinetics, pathogenicity and virus-induced cellular responses of cattle-origin influenza A(H5N1) isolates from Texas, United States.

Ahmed Mostafa1,2,3 Ramya S Barre1 Anna Allué-Guardia4 Ruby A Escobedo1 Vinay Shivanna5 Hussin Rothan1 Esteban M Castro1 Yao Ma1 Anastasija Cupic6,7 Nathaniel Jackson1 Mahmoud Bayoumi1,8 Jordi B Torrelles3,4 Chengjin Ye1 Adolfo García-Sastre6,9,10,11,12,13 Luis Martinez-Sobrido1
Affiliations 13 institutions
  1. Host-pathogen interactions (HPI) and Disease Intervention and Prevention (DIP) programs, Texas Biomedical Research Institute, San Antonio, TX, USA.
  2. Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza, Egypt.
  3. International Center for the Advancement of Research and Education (I•CARE), Texas Biomedical Research Institute, San Antonio, TX, USA.
  4. Population Health Program, Tuberculosis Group, Texas Biomedical Research Institute, San Antonio, TX, USA.
  5. Southwest National Primate Research Center at the Texas Biomedical Research Institute, San Antonio, TX, USA.
  6. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  7. Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  8. Virology Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
  9. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  10. Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  11. The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  12. Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  13. The Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
PMID39727152 DOI10.1080/22221751.2024.2447614 Year2025 Journal Emerging microbes & infections Emerg Microbes Infect Languageeng Statusppublish

Abstract

The host range of HPAIV H5N1 was recently expanded to include ruminants, particularly dairy cattle in the United States (US). Shortly after, human H5N1 infection was reported in a dairy worker in Texas following exposure to infected cattle. Herein, we rescued the cattle-origin influenza A/bovine/Texas/24-029328-02/2024(H5N1, rHPbTX) and A/Texas/37/2024(H5N1, rHPhTX) viruses, identified in dairy cattle and human, respectively, and their low pathogenic forms, rLPbTX and rLPhTX, with monobasic HA cleavage sites. Intriguingly, rHPhTX replicated more efficiently than rHPbTX in mammalian and avian cells. Still, variations in the PA and NA proteins didn't affect their antiviral susceptibility to PA and NA inhibitors. Unlike rHPbTX and rLPbTX, both rHPhTX and rLPhTX exhibited higher pathogenicity and efficient replication in infected C57BL/6J mice. The lungs of rHPhTX-infected mice produced higher inflammatory cytokines/chemokines than rHPbTX-infected mice. Our results highlight the potential risk of HPAIV H5N1 virus adaptation in human and/or dairy cattle during the current multistate/multispecies outbreak in the US.

Supporting text Virus Host Location
adaptation 13 Cattle H5N1 virus 1 HPAIV 6 pathogenicity 54 zoonosis 116 Influenza A Virus, H5N1 Subtype 300 Mice, Inbred C57BL 21 Orthomyxoviridae Infections 228 Virus Replication 191 Animals 1948 Cattle 126 Cattle Diseases 47 Cytokines 12 Dogs 176 Female 289 Host Specificity 132 Humans 1440 Influenza, Human 286 Kinetics 8 Lung 65 Madin Darby Canine Kidney Cells 36 Mice 253 Texas 14 Virulence 108

Evidence records

2 total
Transmission Evidence
1 records · 1 evidence types
Evidence type Spillover Event
1 records
OVE8702 Spillover Event
Key finding

A human H5N1 infection occurred in a dairy worker in Texas following exposure to infected cattle, indicating an animal-to-human spillover event.

Virus
Influenza A virus H5N1
Host
human Homo sapiens Natural host domestic cattle Bos taurus Natural host
Location
United States
Supporting text

Shortly after, human H5N1 infection was reported in a dairy worker in Texas following exposure to infected cattle.

Method
case investigation | exposure history assessment | virus identification
Study design
epidemiological observation of natural spillover event
Transmission direction
animal-to-human
Geographic raw
Texas | United States
Country inferred
USA
Experimental Infection
1 records · 1 evidence types
Evidence type Pathogenicity Experiment
1 records
OVE8700 Pathogenicity Experiment
Key finding

rHPhTX and rLPhTX viruses caused higher pathogenicity and more efficient replication than rHPbTX and rLPbTX in experimentally infected C57BL/6J mice.

Virus
Influenza A virus H5N1
Host
house mouse Mus musculus Experimental system
Location
Not specified
Supporting text

Unlike rHPbTX and rLPbTX, both rHPhTX and rLPhTX exhibited higher pathogenicity and efficient replication in infected C57BL/6J mice.

Method
experimental infection of mice | comparison of replication efficiency and disease severity
Experimental system
mouse infection model