MINI REVIEW article
Front. Cell. Infect. Microbiol.
Sec. Veterinary and Zoonotic Infection
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1625665
Emerging Threats of H5N1 Clade 2.3.4.4b: Cross-Species Transmission, Pathogenesis, and Pandemic Risk
Provisionally accepted
Muhammad Azeem RiazYing-Shi YangSehrish Siddique
Chun-Wei Shi
Gui-Lian YangTeerath Kumar Suthar
Wen-Tao Yang*
Chun-Feng Wang- College of Animal Science and Technology, Jilin Agriculture University, Changchun, China
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H5N1 is a highly pathogenic avian influenza virus (HPAIV) with zoonotic potential, posing a significant risk to animal health, agriculture, and human public health. A particular strain, clade 2.3.4.4b, has spread globally and has been detected in various mammalian species-including cattle and a limited number of human caseshighlighting its potential to spark a pandemic. Investigating this specific clade represents a crucial step toward the development of effective preventive and therapeutic strategies. This mini-review aims to outline the etiology and pathophysiological mechanisms driving the current bird flu outbreak in cattle. A targeted literature search was conducted in PubMed for studies published between 2003 and 2025 using keywords such as "bird flu", "cattle", "mammals", "H5N1", and "pathogenesis". This review explores the pathogenic mechanisms and clinical manifestations associated with HPAIV H5N1 infections in mammals sepecially in cattle. A key hypothesis is that the ongoing outbreak is fueled by molecular adaptations in the virus that enhance its ability to cross species barriers. As these mechanisms continue to be uncovered, there is a pressing need for high-quality research to inform pandemic preparedness, guide effective control strategies, and support the development of targeted vaccines and antiviral therapies.
Keywords: Cattle, cross-species barrier, HPAIV H5N1, Mammals, Molecular adaptations, Reassortment
Received: 15 May 2025; Accepted: 19 Jun 2025.
Copyright: © 2025 Riaz, Yang, Siddique, Shi, Yang, Suthar, Yang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wen-Tao Yang, College of Animal Science and Technology, Jilin Agriculture University, Changchun, China
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