The Smidt Heart Institute and the Barbra Streisand Women's Heart Center, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
The Integrated Regenerative Research Institute (IRRI) at San Diego State University San Diego State University, San Diego, CA, United States.
Virology. 2019 Mar;529:169-176. doi: 10.1016/j.virol.2019.01.025. Epub 2019 Jan 30.
Coxsackievirus B is a significant human pathogen and is a leading cause of myocarditis. We and others have observed that certain enteroviruses including coxsackievirus B cause infected cells to shed extracellular vesicles containing infectious virus. Recent reports have shown that vesicle-bound virus can infect more efficiently than free virus. Though microRNAs are differentially regulated in cells following infection, few have been associated with the vesicles shed from infected cells. Here we report exclusive trafficking of specific microRNAs into viral vesicles compared to vesicles from non-infected cells. We found that the most highly-expressed unique microRNA in viral vesicles was miR-590-5p, which facilitates prolonged viral replication by blocking apoptotic factors. Cells over-expressing this miR were significantly more susceptible to infection. This may be a mechanism by which coxsackievirus B boosts subsequent rounds of infection by co-packaging virus and a select set of pro-viral microRNAs in extracellular vesicles.
柯萨奇病毒 B 是一种重要的人类病原体，也是心肌炎的主要病因。我们和其他人观察到，某些肠道病毒，包括柯萨奇病毒 B，会导致感染细胞释放含有传染性病毒的细胞外囊泡。最近的报告表明，囊泡结合的病毒比游离病毒更能有效地感染。尽管感染后细胞中的 microRNAs 会发生差异调节，但很少有 microRNAs 与感染细胞释放的囊泡有关。在这里，我们报告了特定的 microRNAs 与非感染细胞释放的囊泡相比，被专门转运到病毒囊泡中。我们发现，病毒囊泡中表达水平最高的独特 microRNA 是 miR-590-5p，它通过阻断凋亡因子促进病毒的复制。过度表达这种 miR 的细胞对感染的敏感性显著增加。这可能是柯萨奇病毒 B 通过在细胞外囊泡中共同包装病毒和一组选定的促病毒 microRNAs 来增强后续轮次感染的机制之一。
