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向细胞透的乙型肝炎病毒核心蛋白变体作为潜在的抗病毒剂

Sanaa Bendahmane¹, Marie Follo², Fuming Zhang³

¹Private Faculty of Health Professions and Technologies, Private University of Marrakech, Marrakech 42312, Morocco.

|September 28, 2024

概括

蛋白质转导域 (PTD) 被添加到B型肝炎病毒 (HBV) 核心蛋白质融合中,以增强直接向细胞输送蛋白质. 基本的PTD和一种新的HBV核心蛋白域显示出有希望的细胞吸收抗病毒策略.

科学领域:

病毒学病毒学
分子生物学分子生物学
生物化学生物化学

背景情况:

乙型肝炎病毒 (HBV) 感染是一个重大的全球健康挑战,治疗干预措施有限.
目前的抗病毒策略包括新的方法,如融合蛋白,如Staphylococcus aureus核酶 (SN) 与HBV核心蛋白 (HBc) 融合,称为coreSN.
以前的coreSN表达依赖于等离子体转染,限制了直接蛋白质递送应用.

研究的目的:

研究将蛋白质转导域 (PTD) 纳入光核心SN模型以直接向细胞输送蛋白质的潜力.
为了评估与核心SN蛋白质融合的不同PTD所赋予的细胞透性质.
探索新型PTDs的疗效,包括来自HBV本身的PTDs,以增强细胞吸收.

主要方法:

通过将四个不同的PTD (TLM,Tat4,NP,NS) 插入HBc序列的两个位置来构建融合蛋白,以绿色光蛋白 (GFP) 取代SN用于可视化.
蛋白质被表达在大肠杆菌中,它们的结合和被人类细胞吸收被使用流细胞计和光显微镜评估.
还评估了三倍化Simian virus 40 (SV40) 大T抗原核定位信号 (NLS) 对吸收的影响.

主要成果:

该研究表明了PTD依赖的相互作用和细胞吸收的融合蛋白.
基本的PTDs,特别是Tat4,NP和NS,显示出细胞吸收的显著证据.
通过添加SV40 NLS,吸收进一步增强,有趣的是,HBV核心蛋白质的C终端域本身表现出新的PTD活性.

结论:

将PTD引入coreSN融合蛋白质可以赋予细胞透性质,使直接的蛋白质输送成为可能.
基本的PTD和HBV核心蛋白的C端域在促进细胞吸收方面是有效的.
这些发现支持细胞透性病毒囊蛋白融合的进一步发展,作为抗病毒疗法的有前途战略.

关键词:

肝炎病毒核心蛋白质是HBV的核心蛋白质.细胞透的.细胞吸收机制的机制药物输送是药物输送的过程.肝硫酸盐蛋白质糖是一种蛋白质糖.蛋白质转导域是蛋白质的转导域.

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