Caspase cleavage of influenza A virus M2 disrupts M2-LC3 interaction and regulates virion production.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-03 DOI:10.1038/s44319-025-00388-7

Carmen Figueras-Novoa, Masato Akutsu, Daichi Murata, Anne Weston, Ming Jiang, Beatriz Montaner, Christelle Dubois, Avinash Shenoy, Rupert Beale

引用次数: 0

Abstract

Influenza A virus (IAV) Matrix 2 protein (M2) is an ion channel, required for efficient viral entry and egress. M2 interacts with the small ubiquitin-like LC3 protein through a cytoplasmic C-terminal LC3-interacting region (LIR). Here, we report that M2 is cleaved by caspases, abolishing the M2-LC3 interaction. A crystal structure of the M2 LIR in complex with LC3 indicates the caspase cleavage tetrapeptide motif (₈₂SAVD₈₅) is an unstructured linear motif that does not overlap with the LIR. IAV mutant expressing a permanently truncated M2, mimicking caspase cleavage, exhibit defects in M2 plasma membrane transport, viral filament formation, and virion production. Our results reveal a dynamic regulation of the M2-LC3 interaction by caspases. This highlights the role of host proteases in regulating IAV exit, relating virion production with host cell state.

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甲型流感病毒M2的Caspase切割破坏了M2- lc3相互作用并调节病毒粒子的产生。

甲型流感病毒（IAV）基质2蛋白（M2）是一种离子通道，是病毒有效进出所必需的。M2通过细胞质c端LC3相互作用区（LIR）与小的泛素样LC3蛋白相互作用。在这里，我们报道了M2被半胱天冬酶切割，从而消除了M2- lc3相互作用。M2 LIR与LC3复合物的晶体结构表明，caspase裂解四肽基序（82SAVD85）是一个非结构化的线性基序，与LIR不重叠。IAV突变体表达永久截短的M2，模拟caspase切割，在M2质膜运输、病毒丝形成和病毒粒子产生方面表现出缺陷。我们的研究结果揭示了半胱天冬酶对M2-LC3相互作用的动态调节。这突出了宿主蛋白酶在调节IAV退出中的作用，将病毒粒子的产生与宿主细胞状态联系起来。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

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