ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Veterinary and Zoonotic Infection
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1647283
This article is part of the Research TopicUnveiling Host-Pathogen Interactions: Insights into Animal Cellular Immunity and Novel Diagnostics - Volume IIView all 18 articles
CD147 Mediates the Adsorption of Influenza A Virus on the Cell Surface Through Direct Interaction with HA
Provisionally accepted
Ting Wang1,2,3Lei Cao2,3,4Yufei Zhang2,4Chuxing Cheng1,2,3
Haiying Mao1,2,3Xiaotong Hu1,2,3Xiaomei Sun1,2,3Kun Huang1,2,3*
Meilin Jin1,2,3,5*- 1Huazhong Agricultural University, State Key Laboratory of Agricultural Microbiology, Wuhan, China
- 2College of Animal Medicine, Huazhong Agricultural University, Wuhan, China
- 3Center for Cross-disciplinary in Animal Epidemic and Public Health, Hubei Jiangxia Laboratory, Wuhan, China
- 4State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China
- 5National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China
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The adsorption of avian influenza virus (AIV) initiates the viral lifecycle, determining host tropism and pathogenicity. In addition to the classical AIV receptor, auxiliary receptors also play important roles in viral adsorption, though these remains to be fully elucidated. In this study, we identified 25 avian membrane proteins that interact with H5N6 hemagglutinin (HA), one of which, CD147, was confirmed to play a crucial role in promoting AIV adsorption and replication through overexpression and knockout experiments in DF1 and A549 cells. As a highly glycosylated transmembrane protein, CD147 was further shown to directly bind to the HA receptor-binding domain via its extracellular immunoglobulin-like domains, independently of its glycosylation, thereby mediating viral adsorption. Moreover, AIV infection upregulated the hyperglycosylated form (HG-CD147), while glycosylation inhibitors reduced viral adsorption, highlighting the role of glycosylation in modulating CD147 function. Finally, disrupting the CD147-HA interaction with soluble proteins or monoclonal antibodies inhibited viral adsorption and replication. This study identifies CD147 as an adjuvant receptor that promotes influenza virus adsorption and provides a mechanistic foundation basis for developing broad-spectrum therapeutics targeting HA-host protein interactions.
Keywords: Avian Influenza Virus (AIV), Hemagglutinin (HA), CD147, Viral adsorption, hostpathogen interaction, Influenza A virus
Received: 15 Jun 2025; Accepted: 07 Aug 2025.
Copyright: © 2025 Wang, Cao, Zhang, Cheng, Mao, Hu, Sun, Huang and Jin. 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:
Kun Huang, Huazhong Agricultural University, State Key Laboratory of Agricultural Microbiology, Wuhan, China
Meilin Jin, National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China
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