登革热和寨卡病毒感染过程中stt3a介导的巨量蛋白复合物组装

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-04-28 DOI:10.1016/j.isci.2025.112535

Tao Liu , Natasha W. Hanners , Huangheng Tao , Claudia Szabo , Dao Xu , Wei Lin , John W. Schoggins , Nan Yan , Jianjun Wu

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引用次数: 0

摘要

黄病毒在哺乳动物细胞中的复制需要宿主寡糖转移酶（OST）复合物，该复合物通常催化蛋白质n -糖基化。然而，黄病毒感染并不需要OST的酶活性，这使得潜在的机制令人费解。我们发现OST的STT3A亚复合物，包括STT3A和DC2，是登革热病毒（DENV）和寨卡病毒（ZIKV）感染所必需的。我们发现，在DENV感染期间，STT3A通过与其他OST亚基、转座子蛋白和病毒非结构蛋白的相互作用，形成一个巨蛋白复合物组装体作为支架。这种巨蛋白复合物的完整性对于支持黄病毒感染是重要的。我们还发现了一种小分子化合物NSC-323241，它可以破坏stt3a介导的巨蛋白复合物组装，并有效阻断DENV和ZIKV感染。总之，我们的研究通过对多亚基OST复合体及相关宿主和病毒蛋白的全面分子解剖，揭示了STT3A在黄病毒感染中的支架功能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

STT3A-mediated mega protein complex assembly during dengue and Zika virus infection

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STT3A-mediated mega protein complex assembly during dengue and Zika virus infection

Flavivirus replication in mammalian cells requires host oligosaccharyltransferase (OST) complex, which is classically known to catalyze protein N-glycosylation. However, enzymatic activity of OST is not required for flavivirus infection, leaving the underlying mechanism puzzling. We show the STT3A sub-complex of OST, including STT3A and DC2, to be critically required for dengue virus (DENV) and Zika virus (ZIKV) infection. We find that STT3A nucleates a mega protein complex assembly during DENV infection as a scaffold through its interaction with other OST subunits, translocon proteins, and viral nonstructural proteins. The integrity of this mega protein complex is important for supporting flavivirus infection. We also identified a small-molecule compound NSC-323241 that disrupts STT3A-mediated mega protein complex assembly and potently blocks DENV and ZIKV infection. Together, our study reveals a scaffolding function of STT3A in flavivirus infection through comprehensive molecular dissection of the multi-subunit OST complex and associated host and viral proteins.

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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