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γ干扰素通过减小唾液酸簇大小来抑制甲型流感病毒的细胞附着。

Interferon-gamma inhibits influenza A virus cellular attachment by reducing sialic acid cluster size.

作者信息

Fong Carol Ho-Yan, Lu Lu, Chen Lin-Lei, Yeung Man-Lung, Zhang Anna Jinxia, Zhao Hanjun, Yuen Kwok-Yung, To Kelvin Kai-Wang

机构信息

State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.

Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Island, People's Republic of China.

出版信息

iScience. 2022 Mar 6;25(4):104037. doi: 10.1016/j.isci.2022.104037. eCollection 2022 Apr 15.

DOI:10.1016/j.isci.2022.104037
PMID:35330686
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8938289/
Abstract

The mucosal antiviral role of type I and III interferon in influenza virus infection is well established. However, much less is known about the antiviral mechanism of type II interferon (interferon-gamma). Here, we revealed an antiviral mechanism of interferon-gamma by inhibiting influenza A virus (IAV) attachment. By direct stochastic optical reconstruction microscopy, confocal microscopy, and flow cytometry, we have shown that interferon-gamma reduced the size of α-2,3 and α-2,6-linked sialic acid clusters, without changing the sialic acid or epidermal growth factor receptor expression levels, or the sialic acid density within cluster on the cell surface of A549 cells. Reversing the effect of interferon-gamma on sialic acid clustering by jasplakinolide reverted the cluster size, improved IAV attachment and replication. Our findings showed the importance of sialic acid clustering in IAV attachment and infection. We also demonstrated the interference of sialic acid clustering as an anti-IAV mechanism of IFN-gamma for IAV infection.

摘要

I型和III型干扰素在流感病毒感染中的黏膜抗病毒作用已得到充分证实。然而，关于II型干扰素（干扰素-γ）的抗病毒机制却知之甚少。在此，我们揭示了干扰素-γ通过抑制甲型流感病毒（IAV）附着的抗病毒机制。通过直接随机光学重建显微镜、共聚焦显微镜和流式细胞术，我们发现干扰素-γ减小了α-2,3和α-2,6连接的唾液酸簇的大小，而不改变A549细胞表面唾液酸或表皮生长因子受体的表达水平，也不改变簇内唾液酸的密度。用茉莉素内酯逆转干扰素-γ对唾液酸聚集的影响可恢复簇的大小，改善IAV的附着和复制。我们的研究结果表明唾液酸聚集在IAV附着和感染中的重要性。我们还证明了唾液酸聚集的干扰是IFN-γ针对IAV感染的一种抗IAV机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/78e7f051aa44/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/97c0bfe245a8/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/8e49a20acb09/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/b2422cf34493/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/c43f8daaad26/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/8d880752d22a/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/9c145b4ba675/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/d0a0b809dfcc/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/b38dacf37854/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/3f5b0db5c624/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/78e7f051aa44/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/97c0bfe245a8/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/8e49a20acb09/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/b2422cf34493/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/c43f8daaad26/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/8d880752d22a/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/9c145b4ba675/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/d0a0b809dfcc/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/b38dacf37854/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/3f5b0db5c624/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb2/8938289/78e7f051aa44/gr9.jpg

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