MβCD inhibits SFTSV entry by disrupting lipid raft structure of the host cells

IF 4.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Antiviral research Pub Date : 2024-09-10 DOI:10.1016/j.antiviral.2024.106004

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Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV), recently named as Dabie bandavirus, belongs to the family Phenuiviridae of the order Bunyavirales, is a newly-identified bunyavirus with a case fatality rate of up to 30%, posing a serious threat to public health. Lipid rafts on plasm membranes are important for the entry of enveloped viruses; however, the role of lipid rafts in bunyavirus entry remains unclear. In this study, we found that methyl-beta-cyclodextrin (MβCD), a drug that disrupts cholesterol in lipid rafts of cell membranes, inhibits SFTSV infection. Additionally, there is a back-complementary effect of SFTSV infection upon the addition of cholesterol. Moreover, the concentration of SFTSV particles in lipid rafts during entry directly indicated the role of lipid rafts as a gateway, whereas MβCD could inhibit SFTSV entry by affecting the structure of lipid rafts. In an in vivo study, MβCD also reduced the susceptibility of mice to SFTSV infection. Our results suggest that SFTSV can interact with Talin1 proteins on lipid rafts to enter host cells by endocytosis of lipid rafts and reveal the potential therapeutic value of MβCD for SFTSV infection.

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MβCD 通过破坏宿主细胞的脂质筏结构抑制 SFTSV 的进入

严重发热伴血小板减少综合征病毒（SFTSV）最近被命名为达比带状疱疹病毒，属于布尼亚病毒科布尼亚病毒属，是一种新发现的布尼亚病毒，病死率高达30%，对公共卫生构成严重威胁。质膜上的脂质筏对包膜病毒的进入非常重要，但脂质筏在布尼亚病毒进入中的作用仍不清楚。在这项研究中，我们发现甲基-β-环糊精（MβCD）这种能破坏细胞膜脂质筏中胆固醇的药物能抑制 SFTSV 的感染。此外，加入胆固醇后，SFTSV 的感染会出现反补效应。此外，SFTSV 颗粒在进入过程中在脂质筏中的浓度直接表明了脂质筏作为网关的作用，而 MβCD 可以通过影响脂质筏的结构来抑制 SFTSV 的进入。在一项体内研究中，MβCD还降低了小鼠对SFTSV感染的易感性。我们的研究结果表明，SFTSV能与脂质筏上的Talin1蛋白相互作用，通过脂质筏的内吞作用进入宿主细胞，并揭示了MβCD对SFTSV感染的潜在治疗价值。

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

Antiviral research 医学-病毒学

CiteScore

17.10

自引率

3.90%

发文量

157

审稿时长

34 days

期刊介绍： Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.

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