Outcomes of experimental infection of calves with swine influenza H3N2 virus

ABSTRACT Unprecedented outbreaks caused by the H5N1 highly pathogenic avian influenza virus (HPAIV) among dairy cows in the United States have raised significant concerns. Whether other subtypes of influenza A viruses (IAVs) can infect and transmit in cattle remains largely unknown. Herein, we infec...

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Main Authors: Lei Shi, Yuekun Lang, Sawrab Roy, Zhenyu Shen, Dipali Gupta, Chao Dai, Muhammad Afnan Khalid, William J. Mitchell, Shuping Zhang, Richard Webby, Juergen Richt, Wenjun Ma
Format: Article
Language:English
Published: American Society for Microbiology 2025-07-01
Series:mBio
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Online Access:https://journals.asm.org/doi/10.1128/mbio.03957-24
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author Lei Shi
Yuekun Lang
Sawrab Roy
Zhenyu Shen
Dipali Gupta
Chao Dai
Muhammad Afnan Khalid
William J. Mitchell
Shuping Zhang
Richard Webby
Juergen Richt
Wenjun Ma
author_facet Lei Shi
Yuekun Lang
Sawrab Roy
Zhenyu Shen
Dipali Gupta
Chao Dai
Muhammad Afnan Khalid
William J. Mitchell
Shuping Zhang
Richard Webby
Juergen Richt
Wenjun Ma
author_sort Lei Shi
collection DOAJ
description ABSTRACT Unprecedented outbreaks caused by the H5N1 highly pathogenic avian influenza virus (HPAIV) among dairy cows in the United States have raised significant concerns. Whether other subtypes of influenza A viruses (IAVs) can infect and transmit in cattle remains largely unknown. Herein, we infected cattle respiratory and mammary gland cells with different IAVs and two groups of Holstein calves intranasally or orally with a swine H3N2 virus to determine their susceptibility. Naive calves were co-housed with infected animals to investigate virus transmission. Results showed that tested swine and avian IAVs could infect cattle primary nasal turbinate and tracheal epithelial cells, as well as immortalized mammary gland epithelial cells and fibroblasts. No obvious clinical signs, including fever, were observed in infected and contact calves, but macroscopic lung lesions were found in necropsied animals in both groups on day 5 post-infection. Viral shedding was detected in three out of four nasally infected calves but not in orally infected or the two groups of contact animals. Interestingly, viral RNA and antigen could not be detected in all tissues from individual necropsied animals from either infection group, but viral RNA and sequences were detected in serum samples of two nasally infected calves on day 7 post-infection, not on other days and in other animals. Additionally, only the nasally infected animals seroconverted. Our results indicate that in addition to H5N1 HPAIV, swine H3N2 virus can infect cattle but does not transmit efficiently among them, suggesting that other subtypes of IAVs could infect and replicate in cattle.IMPORTANCEHighly pathogenic avian influenza H5N1 virus outbreaks in U.S. dairy herds have raised questions about whether other subtypes of influenza A viruses (IAVs) can infect and transmit in cattle. In this study, we investigated the susceptibility and infection of different IAVs in bovine primary and immortalized cells and Holstein calves. Results showed that avian H5N1 and H9N2, and swine H3N2 IAVs could infect beef cattle primary nasal turbinate and tracheal epithelial cells, as well as immortalized mammary gland epithelial cells and fibroblasts. Moreover, the swine H3N2 could infect the calves through intranasal infection, but not through oral infection, despite no obvious clinical signs and efficient transmission being observed. Our results demonstrate that other subtypes of IAVs can infect cattle and might pose threats to public and animal health.
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spelling doaj-art-43b7dbc4a0074f0db46d2de9125cf64e2025-08-20T02:36:16ZengAmerican Society for MicrobiologymBio2150-75112025-07-0116710.1128/mbio.03957-24Outcomes of experimental infection of calves with swine influenza H3N2 virusLei Shi0Yuekun Lang1Sawrab Roy2Zhenyu Shen3Dipali Gupta4Chao Dai5Muhammad Afnan Khalid6William J. Mitchell7Shuping Zhang8Richard Webby9Juergen Richt10Wenjun Ma11Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USADepartment of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USADepartment of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USADepartment of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USADepartment of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USADepartment of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USADepartment of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USADepartment of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USADepartment of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USADepartment of Host-Microbe Interactions, St Jude Children's Research Hospital, Memphis, Tennessee, USADepartment of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas, USADepartment of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USAABSTRACT Unprecedented outbreaks caused by the H5N1 highly pathogenic avian influenza virus (HPAIV) among dairy cows in the United States have raised significant concerns. Whether other subtypes of influenza A viruses (IAVs) can infect and transmit in cattle remains largely unknown. Herein, we infected cattle respiratory and mammary gland cells with different IAVs and two groups of Holstein calves intranasally or orally with a swine H3N2 virus to determine their susceptibility. Naive calves were co-housed with infected animals to investigate virus transmission. Results showed that tested swine and avian IAVs could infect cattle primary nasal turbinate and tracheal epithelial cells, as well as immortalized mammary gland epithelial cells and fibroblasts. No obvious clinical signs, including fever, were observed in infected and contact calves, but macroscopic lung lesions were found in necropsied animals in both groups on day 5 post-infection. Viral shedding was detected in three out of four nasally infected calves but not in orally infected or the two groups of contact animals. Interestingly, viral RNA and antigen could not be detected in all tissues from individual necropsied animals from either infection group, but viral RNA and sequences were detected in serum samples of two nasally infected calves on day 7 post-infection, not on other days and in other animals. Additionally, only the nasally infected animals seroconverted. Our results indicate that in addition to H5N1 HPAIV, swine H3N2 virus can infect cattle but does not transmit efficiently among them, suggesting that other subtypes of IAVs could infect and replicate in cattle.IMPORTANCEHighly pathogenic avian influenza H5N1 virus outbreaks in U.S. dairy herds have raised questions about whether other subtypes of influenza A viruses (IAVs) can infect and transmit in cattle. In this study, we investigated the susceptibility and infection of different IAVs in bovine primary and immortalized cells and Holstein calves. Results showed that avian H5N1 and H9N2, and swine H3N2 IAVs could infect beef cattle primary nasal turbinate and tracheal epithelial cells, as well as immortalized mammary gland epithelial cells and fibroblasts. Moreover, the swine H3N2 could infect the calves through intranasal infection, but not through oral infection, despite no obvious clinical signs and efficient transmission being observed. Our results demonstrate that other subtypes of IAVs can infect cattle and might pose threats to public and animal health.https://journals.asm.org/doi/10.1128/mbio.03957-24cattle respiratory and mammary gland cellscalvesswine and avian influenza virusesinfectiontransmission
spellingShingle Lei Shi
Yuekun Lang
Sawrab Roy
Zhenyu Shen
Dipali Gupta
Chao Dai
Muhammad Afnan Khalid
William J. Mitchell
Shuping Zhang
Richard Webby
Juergen Richt
Wenjun Ma
Outcomes of experimental infection of calves with swine influenza H3N2 virus
mBio
cattle respiratory and mammary gland cells
calves
swine and avian influenza viruses
infection
transmission
title Outcomes of experimental infection of calves with swine influenza H3N2 virus
title_full Outcomes of experimental infection of calves with swine influenza H3N2 virus
title_fullStr Outcomes of experimental infection of calves with swine influenza H3N2 virus
title_full_unstemmed Outcomes of experimental infection of calves with swine influenza H3N2 virus
title_short Outcomes of experimental infection of calves with swine influenza H3N2 virus
title_sort outcomes of experimental infection of calves with swine influenza h3n2 virus
topic cattle respiratory and mammary gland cells
calves
swine and avian influenza viruses
infection
transmission
url https://journals.asm.org/doi/10.1128/mbio.03957-24
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