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鉴定抗 HSV1 ICP47 蛋白质抑制的 TAP2 蛋白质变体

Gregory Nagy¹, Rebecca Presley¹, Shruti Dhar¹

¹Department of Biomedical Informatics and the OSU Comprehensive Cancer Center, The Ohio State University, Columbus, OH.

bioRxiv : the preprint server for biology

|November 28, 2024

概括

疹简单病毒1使用ICP47来阻止与抗原处理 (TAP) 相关的载体对抗原的呈现. 研究人员确定了三种抗 ICP47 的 TAP2 变种,为抗病毒免疫逃避提供了新的策略.

科学领域:

免疫学免疫学免疫学
病毒学病毒学
分子生物学分子生物学

背景情况:

简单疹病毒1 (HSV-1) 通过表达ICP47.7来逃避宿主免疫力.
ICP47抑制与抗原处理相关的载体 (TAP),这是抗原呈现的关键组成部分.
TAP是一种异构体,有TAP1和TAP2的子单元.

研究的目的:

为了识别TAP2的变体,耐受HSV-1的ICP47.7的抑制.
为了从功能上区分参与结与ICP47结合的TAP2残留物.
探索预防病毒免疫逃避的潜在治疗点.

主要方法:

对1786个TAP2变种的库进行选,以检测对ICP47.7的耐药性.
对有前途的TAP2变种进行单独测试.
与ICP47和结位相关的TAP2残留物的结构分析.

主要成果:

鉴定了39种对ICP47抑制有抗性的TAP2变异.
确认了具有显著耐药性的三个变种 (T257I,S274H,T244R).
观察到耐药性是特定于ICP47,而不是爱斯坦巴尔病毒BNLF2a.
在ICP47结合部位附近局部化的耐药残留物,在结合部位附近的Ser274.

结论:

从功能上解决的TAP2残留物对于结合至关重要,而对于ICP47结合至关重要.
确定了特定的TAP2残留物,如果准,可以阻止抗原处理的病毒下调.
为开发抗疹病毒免疫规避策略的小分子抑制剂提供了基础.

关键词:

抗原呈现方式简单疹病毒1 简单疹病毒在 ICP4747 中,主要组织相容性复合物I类.与抗原处理相关的传送器.免疫逃避免疫逃避

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相关概念视频

Herpes

Herpes

Herpes simplex type 1 (HSV‑1) is a widespread pathogen responsible for orolabial lesions. It is an enveloped, double-stranded DNA (dsDNA) virus belonging to the family Herpesviridae. Once the virus infects a host cell, its double‑stranded DNA genome is delivered into the nucleus, where a coordinated cascade of immediate‑early, early, and late gene expression directs viral DNA replication, structural protein synthesis, and virion assembly. After primary infection of epithelial cells, HSV-1...