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雪貂干扰素诱导跨膜蛋白 1 对甲型流感病毒的诱导及抗病毒活性。

Induction and antiviral activity of ferret myxovirus resistance (Mx) protein 1 against influenza A viruses.

机构信息

Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, 792 Elizabeth St., Victoria, 3000, Australia.

Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, 53127, Bonn, Germany.

出版信息

Sci Rep. 2024 Jun 12;14(1):13524. doi: 10.1038/s41598-024-63314-2.

DOI:10.1038/s41598-024-63314-2
PMID:38866913
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11169552/
Abstract

Myxovirus resistance (Mx) proteins are products of interferon stimulated genes (ISGs) and Mx proteins of different species have been reported to mediate antiviral activity against a number of viruses, including influenza A viruses (IAV). Ferrets are widely considered to represent the 'gold standard' small animal model for studying pathogenesis and immunity to human IAV infections, however little is known regarding the antiviral activity of ferret Mx proteins. Herein, we report induction of ferret (f)Mx1/2 in a ferret lung cell line and in airway tissues from IAV-infected ferrets, noting that fMx1 was induced to higher levels that fMx2 both in vitro and in vivo. Overexpression confirmed cytoplasmic expression of fMx1 as well as its ability to inhibit infection and replication of IAV, noting that this antiviral effect of fMx1was modest when compared to cells overexpressing either human MxA or mouse Mx1. Together, these studies provide the first insights regarding the role of fMx1 in cell innate antiviral immunity to influenza viruses. Understanding similarities and differences in the antiviral activities of human and ferret ISGs provides critical context for evaluating results when studying human IAV infections in the ferret model.

摘要

抗粘液病毒（Mx）蛋白是干扰素刺激基因（ISGs）的产物，不同物种的 Mx 蛋白已被报道具有针对多种病毒（包括甲型流感病毒（IAV））的抗病毒活性。雪貂被广泛认为是研究人类 IAV 感染发病机制和免疫的“黄金标准”小动物模型，但对于雪貂 Mx 蛋白的抗病毒活性知之甚少。在此，我们报告了在雪貂肺细胞系和 IAV 感染的雪貂气道组织中诱导雪貂（f）Mx1/2 的情况，注意到 fMx1 的诱导水平高于 fMx2，无论是在体外还是体内。过表达证实了 fMx1 的细胞质表达及其抑制 IAV 感染和复制的能力，注意到与过表达人 MxA 或鼠 Mx1 的细胞相比，fMx1 的这种抗病毒作用较为温和。总之，这些研究首次提供了关于 fMx1 在细胞固有抗病毒免疫中的作用的见解，以应对在雪貂模型中研究人类 IAV 感染时评估结果的相似性和差异性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ac/11169552/3753a0006f51/41598_2024_63314_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ac/11169552/3753a0006f51/41598_2024_63314_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ac/11169552/e481d8b746e5/41598_2024_63314_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ac/11169552/cb75051f4482/41598_2024_63314_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ac/11169552/cf034a8bb852/41598_2024_63314_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ac/11169552/2eec82aebfd5/41598_2024_63314_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ac/11169552/0cc92915587d/41598_2024_63314_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ac/11169552/cdfd954fe733/41598_2024_63314_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ac/11169552/3753a0006f51/41598_2024_63314_Fig8_HTML.jpg

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