ORIGINAL RESEARCH article
Front. Immunol.
Sec. Viral Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1592841
This article is part of the Research TopicGenetic and Molecular Markers in Viral InfectionsView all 3 articles
Type III interferon, age and IFNL gene single nucleotide polymorphisms (SNPs) determine the characteristics of H1N1 influenza infection
Provisionally accepted
- 1The First Affiliated Hospital, University of South China, Hengyang, China
- 2Biotechnology Institute, Fujian Academy of Agricultural Sciences, Fuzhou, Fujian, China
- 3University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States
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Background: Host factors, such as innate immune response, genetic polymorphisms, age, and body weight are important determinants of susceptibility, severity, and responsiveness to treatment of influenza disease. However, the molecular mechanisms underlying these clinical associations remain poorly characterized, particularly regarding IFN-λ-mediated antiviral responses.Methods: Wild-type mice and IL-28B-/- mice were used to systematically investigate the antiviral and anti-inflammatory functions of IL-29 or IL-28, respectively. Plaque assay and DNA genotyping were conducted to determine the correlations between IFN-λ polymorphisms and H1N1 infection outcomes. ELISA, Real-time PCR and luciferase reporter assays were carried out to explore the mechanism.Results: IFN-λ plays an important antiviral and immunoprotective role in H1N1 infection. Specifically, IL-29 and IL-28 exhibit important dual antiviral and anti-inflammaroty roles. Age factor also affects H1N1 clearance and therapeutic responsiveness. Human alveolar epithelial cells (AECs) from young donors support higher H1N1 replication and weak response to antiviral treatment with IL-29. Rs12979860 (IL-28 C/T), rs8099917 (IL-28 T/G) and rs30461 (IL-29 A/G), the three identified single nucleotide polymorphisms (SNPs) in IFNL genes, are also associated with H1N1 outcomes. AECs from rs12979860TT and rs8099917GG donors exhibit higher H1N1 replication and nonresponsiveness to IL-29 antiviral therapy. AECs from rs12979860 TT donors also produce lower levels of IFN and exhibit inhibited promoter activity of IL-29 in response to H1N1 infection. In addition, increased allele frequencies of rs12979860 T and rs8099917 G were associated with higher BMI, another important factor influencing H1N1 susceptibility. Conclusions: This is the first study to comprehensively explore the impact of host factors, especially IFN-λ polymorphisms, on H1N1 virus infection. Further elucidation of the underlying mechanisms may help to develop novel prevention and treatment strategies for influenza virus infection.
Keywords: type III interferon, Single nucleotide polymorphisms, age, Obesity, influenza infection
Received: 13 Mar 2025; Accepted: 22 Apr 2025.
Copyright: © 2025 Zhu, Wang, Guan, Liu and Zhang. 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: Wenbo Zhu, The First Affiliated Hospital, University of South China, Hengyang, China
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