聚皮里米丁管结合蛋白是登革热病毒内部核糖体进入部位的交易因素
Leandro Fernández-García1, Jenniffer Angulo1,2, Marcelo López-Lastra1
1Laboratorio de Virología Molecular, Instituto Milenio de Inmunología e Inmunoterapia, Departamento de Enfermedades Infecciosas e Inmunología Pediátrica, Centro de Investigaciones Médicas, Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago 8330024, Chile.
Viruses
|November 27, 2024
概括
登革热病毒 (DENV) 内部核糖体进入部位 (IRES) 活性由病毒蛋白酶增强. 聚皮里米丁通道结合蛋白 (PTB) 异型PTB1,PTB2和PTB4作为IRES交易因子 (ITAF) 起作用,它们的RNA识别动机具有不同的作用.
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:
- 登革热病毒 (DENV) 是Flaviviridae家族的成员,利用复杂的翻译机制.
- 翻译启动可以通过上盖依赖或内部核糖体进入部位 (IRES) 依赖的途径进行.
- 在某些病毒中,IRES元素对于病毒RNA (vRNA) 的翻译至关重要.
研究的目的:
- 为了研究DENV IRES在BHK-21细胞中的活性.
- 确定聚皮里米丁通道结合蛋白 (PTB) 异型 (PTB1,PTB2,PTB4) 作为DENV IRES的IRES交易因子 (ITAF) 的作用.
- 阐明PTB的RNA识别基因 (RRMs) 中的突变如何影响其ITAF功能.
主要方法:
- 评估了在各种条件下BHK-21细胞中的DENV IRES活性,包括病毒复制和蛋白酶表达.
- 在BHK-21细胞中表达了不同的PTB异型及其突变变体.
- 量化DENV IRES介导的翻译启动使用记者测试.
主要成果:
- 在DENV复制细胞和表达病毒蛋白酶的细胞中刺激了DENV IRES活性 (口疫病毒或人类鼻病毒2A).
- 蛋白酶活性对于DENV IRES刺激至关重要,但不需要完全的上限依赖转化关闭.
- 证实了PTB1,PTB2和PTB4是DENV IRES的ITAF,其中PTB1表现出最强的活动.
- 在PTB的RRMs的突变不同地影响了PTB1,PTB2和PTB4的ITAF活动,表明了特定的RRM角色.
结论:
- DENV IRES的活动是由病毒蛋白酶调节的,需要特定的ITAFs.
- PTB1,PTB2和PTB4是DENV IRES的关键ITAF,对它们的RRMs有不同的功能要求.
- 了解这些相互作用可以了解DENV复制和潜在的治疗点.
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