A Review of Cross-Species Transmission Mechanisms of Influenza Viruses
by
Xianfeng Hui
1,2,3,†, 
Xiaowei Tian
4,†, 
Shihuan Ding
1,2,3,
Ge Gao
2,
Jiyan Cui
1,2,3,
Chengguang Zhang
5,
Tiesuo Zhao
1,3,
Liangwei Duan
2,6 and
Hui Wang
2,6,*
1
Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, China
2
Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang 453003, China
3
Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang 453003, China
4
Department of Pathogenic Biology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, China
5
National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China
6
Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Medical Technology, Xinxiang Medical University, Xinxiang 453003, China
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Vet. Sci. 2025, 12(5), 447; https://doi.org/10.3390/vetsci12050447
Submission received: 9 April 2025
/
Revised: 5 May 2025
/
Accepted: 6 May 2025
/
Published: 7 May 2025
(This article belongs to the Special Issue Viral Crossroads: The Interface Between Wildlife and Domestic Animal Health)
Simple Summary
The cross-species transmission of influenza viruses is pivotal in zoonotic pandemics, driven by viral genetic adaptability, host–receptor compatibility, and ecological factors. Key mutations in hemagglutinin and neuraminidase enable host barrier breaches, while intermediate hosts (e.g., pigs) act as viral “mixers” for strain diversification. Advances in sequencing and structural biology have identified critical molecular markers, yet challenges persist in deciphering dynamic virus–host evolution, establishing real-time surveillance, and designing broad-spectrum interventions. Integrating multidisciplinary strategies—including One Health networks and artificial intelligence-driven prediction models—is crucial for building a multi-layered defense system. This review synthesizes current progress and challenges, offering a framework to optimize pandemic preparedness against influenza spillover risks.
Abstract
The cross-species transmission of influenza viruses represents a critical link in the pandemic of zoonotic diseases. This mechanism involves multi-level interactions, including viral genetic adaptability, host–receptor compatibility, and ecological drivers. Recent studies have highlighted the essential role of mutations in hemagglutinin and neuraminidase in overcoming host barriers, while elucidating the differences in the distribution of host sialic acid receptors. Furthermore, the “mixer” function of intermediate hosts, such as pigs, plays a significant role in viral redistribution. Advances in high-throughput sequencing and structural biology technologies have gradually resolved key molecular markers and host restriction factors associated with these viruses. However, challenges remain in understanding the dynamic evolutionary patterns of virus–host interaction networks, developing real-time early warning capabilities for cross-species transmission, and formulating broad-spectrum prevention and control strategies. Moving forward, it is essential to integrate multidisciplinary approaches to establish a multi-level defense system, leveraging the ‘One Health’ monitoring network, artificial intelligence prediction models, and new vaccine research and development to address the ongoing threat of cross-species transmission of influenza viruses. This paper systematically reviews the research progress and discusses bottlenecks in this field, providing a theoretical foundation for optimizing future prevention and control strategies.
Keywords:
influenza virus; cross-species transmission; mechanisms; One Health
