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Literature detail

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.
PMID 39727152 2025 Emerg Microbes Infect eng ppublish
PubMed DOI Browse context

Article

Publication summary

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.

adaptation Cattle H5N1 virus HPAIV pathogenicity zoonosis Influenza A Virus, H5N1 Subtype Mice, Inbred C57BL Orthomyxoviridae Infections Virus Replication Animals Cattle Cattle Diseases Cytokines Dogs Female Host Specificity Humans Influenza, Human

Structured evidence records

Evidence records

4 total
Host Range Experiment 2 records
Host Range Experiment Extraction confidence 0.85
Key finding

Cattle- and human-origin H5N1 isolates showed differential replication efficiency across mammalian and avian cells and replicated efficiently in mice, indicating expanded host range.

Virus
IAV H5N1
Location
Not specified
Supporting text

rHPhTX replicated more efficiently than rHPbTX in mammalian and avian cells. Unlike rHPbTX and rLPbTX, both rHPhTX and rLPhTX exhibited higher pathogenicity and efficient replication in infected C57BL/6J mice.

Method
replication assay; pathogenicity experiment
Sample type
lung
Experimental system
in vivo animal experiment
Host Range Experiment Extraction confidence 0.85
Key finding

The human H5N1 isolate replicated more efficiently than the bovine H5N1 isolate in mammalian and avian cell cultures, indicating host-dependent adaptation.

Virus
IAV H5N1
Location
Not specified
Supporting text

rHPhTX replicated more efficiently than rHPbTX in mammalian and avian cells.

Method
replication assay
Experimental system
in vitro cell culture
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.90
Key finding

The human-origin H5N1 isolate rHPhTX demonstrated greater replication and pathogenicity than the cattle-origin virus rHPbTX, suggesting molecular adaptation during cross-species transmission.

Virus
IAV H5N1
Host
Not specified
Location
Not specified
Supporting text

Intriguingly, rHPhTX replicated more efficiently than rHPbTX in mammalian and avian cells. Unlike rHPbTX and rLPbTX, both rHPhTX and rLPhTX exhibited higher pathogenicity and efficient replication in infected C57BL/6J 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.

Genes or proteins
PA; NA; HA
Mechanism types
replication_efficiency; pathogenicity; host_adaptation
Spillover Event 1 records
Spillover Event Extraction confidence 0.95
Key finding

A dairy worker in Texas was infected with influenza A(H5N1) after exposure to infected cattle, demonstrating animal-to-human transmission.

Virus
IAV H5N1
Location
United States Texas, United States
Supporting text

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

Study design
case report
Transmission direction
animal-to-human
Geographic raw
Texas
Country inferred
United States