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Derek W Trobaugh¹, Christina L Gardner¹, Chengqun Sun¹

¹Center for Vaccine Research and Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.

|December 20, 2013

概括

微RNA miR-142-3p 限制了马脑炎病毒在骨髓细胞中,但这种限制矛盾地使人类的神经系统疾病恶化. 这种相互作用对于病毒向蚊子传播至关重要.

科学领域:

病毒学病毒学
分子生物学分子生物学
免疫学免疫学免疫学

背景情况:

脊椎动物微RNAs (miRNAs) 在RNA病毒病原性中的作用尚不清楚.
病毒经常发生突变以逃避宿主miRNA介导的抑制.
东部马脑炎病毒 (EEEV) 是蚊子传播的重要人类病原体.

研究的目的:

研究微RNAmiR-142-3p在EEEV.病变发生过程中的作用.
阐明miR-142-3p影响EEEV复制和疾病的机制.
探索miRNA病毒相互作用对病毒传播和宿主免疫力的影响.

主要方法:

在EEEV基因组中分析miR-142-3p结合点.
在具有不同miR-142-3p水平的骨髓系细胞中对EEEV复制的评估.
实体研究评估miR-142-3p限制对EEEV热带性和疾病严重性的影响.
研究miR-142-3p结合区域在蚊子载体能力中的作用.

主要成果:

miR-142-3p通过向病毒RNA的3'非翻译区域,显著限制了骨髓细胞中的EEEV复制.
这种限制限制了髓状细胞中的病毒热流,从而减少了先天免疫反应,并加剧了人类的神经疾病.
在蚊子载体中,miR-142-3p结合部位对于有效的EEEV感染至关重要.

结论:

脊椎动物的miRNAs,如miR-142-3p,可以通过限制特定细胞类型的复制在RNA病毒病原发生中发挥复杂的作用.
这种miRNA介导的限制可以矛盾地增加疾病的严重程度,并促进病毒传播.
RNA病毒可能会进化以利用宿主miRNAs的抗病毒特性来进行自身的传播和传播.

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