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

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/Tex...

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Main Authors: Ahmed Mostafa, Ramya S. Barre, Anna Allué-Guardia, Ruby A. Escobedo, Vinay Shivanna, Hussin Rothan, Esteban M. Castro, Yao Ma, Anastasija Cupic, Nathaniel Jackson, Mahmoud Bayoumi, Jordi B. Torrelles, Chengjin Ye, Adolfo García-Sastre, Luis Martinez-Sobrido
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2024.2447614
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author Ahmed Mostafa
Ramya S. Barre
Anna Allué-Guardia
Ruby A. Escobedo
Vinay Shivanna
Hussin Rothan
Esteban M. Castro
Yao Ma
Anastasija Cupic
Nathaniel Jackson
Mahmoud Bayoumi
Jordi B. Torrelles
Chengjin Ye
Adolfo García-Sastre
Luis Martinez-Sobrido
author_facet Ahmed Mostafa
Ramya S. Barre
Anna Allué-Guardia
Ruby A. Escobedo
Vinay Shivanna
Hussin Rothan
Esteban M. Castro
Yao Ma
Anastasija Cupic
Nathaniel Jackson
Mahmoud Bayoumi
Jordi B. Torrelles
Chengjin Ye
Adolfo García-Sastre
Luis Martinez-Sobrido
author_sort Ahmed Mostafa
collection DOAJ
description 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.
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spelling doaj-art-76bc2c3e2f2c40ac932409aa3bd2d05a2025-01-08T19:18:21ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512025-12-0114110.1080/22221751.2024.2447614Replication kinetics, pathogenicity and virus-induced cellular responses of cattle-origin influenza A(H5N1) isolates from Texas, United StatesAhmed Mostafa0Ramya S. Barre1Anna Allué-Guardia2Ruby A. Escobedo3Vinay Shivanna4Hussin Rothan5Esteban M. Castro6Yao Ma7Anastasija Cupic8Nathaniel Jackson9Mahmoud Bayoumi10Jordi B. Torrelles11Chengjin Ye12Adolfo García-Sastre13Luis Martinez-Sobrido14Host-pathogen interactions (HPI) and Disease Intervention and Prevention (DIP) programs, Texas Biomedical Research Institute, San Antonio, TX, USAHost-pathogen interactions (HPI) and Disease Intervention and Prevention (DIP) programs, Texas Biomedical Research Institute, San Antonio, TX, USAPopulation Health Program, Tuberculosis Group, Texas Biomedical Research Institute, San Antonio, TX, USAHost-pathogen interactions (HPI) and Disease Intervention and Prevention (DIP) programs, Texas Biomedical Research Institute, San Antonio, TX, USASouthwest National Primate Research Center at the Texas Biomedical Research Institute, San Antonio, TX, USAHost-pathogen interactions (HPI) and Disease Intervention and Prevention (DIP) programs, Texas Biomedical Research Institute, San Antonio, TX, USAHost-pathogen interactions (HPI) and Disease Intervention and Prevention (DIP) programs, Texas Biomedical Research Institute, San Antonio, TX, USAHost-pathogen interactions (HPI) and Disease Intervention and Prevention (DIP) programs, Texas Biomedical Research Institute, San Antonio, TX, USADepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USAHost-pathogen interactions (HPI) and Disease Intervention and Prevention (DIP) programs, Texas Biomedical Research Institute, San Antonio, TX, USAHost-pathogen interactions (HPI) and Disease Intervention and Prevention (DIP) programs, Texas Biomedical Research Institute, San Antonio, TX, USAInternational Center for the Advancement of Research and Education (I•CARE), Texas Biomedical Research Institute, San Antonio, TX, USAHost-pathogen interactions (HPI) and Disease Intervention and Prevention (DIP) programs, Texas Biomedical Research Institute, San Antonio, TX, USADepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USAHost-pathogen interactions (HPI) and Disease Intervention and Prevention (DIP) programs, Texas Biomedical Research Institute, San Antonio, TX, USAThe 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.https://www.tandfonline.com/doi/10.1080/22221751.2024.2447614Cattle H5N1 viruszoonosisadaptationpathogenicityHPAIV
spellingShingle Ahmed Mostafa
Ramya S. Barre
Anna Allué-Guardia
Ruby A. Escobedo
Vinay Shivanna
Hussin Rothan
Esteban M. Castro
Yao Ma
Anastasija Cupic
Nathaniel Jackson
Mahmoud Bayoumi
Jordi B. Torrelles
Chengjin Ye
Adolfo García-Sastre
Luis Martinez-Sobrido
Replication kinetics, pathogenicity and virus-induced cellular responses of cattle-origin influenza A(H5N1) isolates from Texas, United States
Emerging Microbes and Infections
Cattle H5N1 virus
zoonosis
adaptation
pathogenicity
HPAIV
title Replication kinetics, pathogenicity and virus-induced cellular responses of cattle-origin influenza A(H5N1) isolates from Texas, United States
title_full Replication kinetics, pathogenicity and virus-induced cellular responses of cattle-origin influenza A(H5N1) isolates from Texas, United States
title_fullStr Replication kinetics, pathogenicity and virus-induced cellular responses of cattle-origin influenza A(H5N1) isolates from Texas, United States
title_full_unstemmed Replication kinetics, pathogenicity and virus-induced cellular responses of cattle-origin influenza A(H5N1) isolates from Texas, United States
title_short Replication kinetics, pathogenicity and virus-induced cellular responses of cattle-origin influenza A(H5N1) isolates from Texas, United States
title_sort replication kinetics pathogenicity and virus induced cellular responses of cattle origin influenza a h5n1 isolates from texas united states
topic Cattle H5N1 virus
zoonosis
adaptation
pathogenicity
HPAIV
url https://www.tandfonline.com/doi/10.1080/22221751.2024.2447614
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