Drury Ruth E, O'Connor Daniel, Pollard Andrew J
Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, Department of Paediatrics, University of Oxford, The Churchill Hospital, Oxford, United Kingdom.
Front Immunol. 2017 Sep 25;8:1182. doi: 10.3389/fimmu.2017.01182. eCollection 2017.
MicroRNAs (miRNAs) are short single-stranded non-coding RNA sequences that posttranscriptionally regulate up to 60% of protein encoding genes. Evidence is emerging that miRNAs are key mediators of the host response to infection, predominantly by regulating proteins involved in innate and adaptive immune pathways. miRNAs can govern the cellular tropism of some viruses, are implicated in the resistance of some individuals to infections like HIV, and are associated with impaired vaccine response in older people. Not surprisingly, pathogens have evolved ways to undermine the effects of miRNAs on immunity. Recognition of this has led to new experimental treatments, RG-101 and Miravirsen-hepatitis C treatments which target host miRNA. miRNAs are being investigated as novel infection biomarkers, and they are being used to design attenuated vaccines, e.g., against Dengue virus. This comprehensive review synthesizes current knowledge of miRNA in host response to infection with emphasis on potential clinical applications, along with an evaluation of the challenges still to be overcome.
微小RNA(miRNA)是短的单链非编码RNA序列,可在转录后调控多达60%的蛋白质编码基因。越来越多的证据表明,miRNA是宿主对感染反应的关键介质,主要通过调控参与固有免疫和适应性免疫途径的蛋白质来实现。miRNA可以控制某些病毒的细胞嗜性,与一些个体对HIV等感染的抵抗力有关,还与老年人疫苗反应受损有关。毫不奇怪,病原体已经进化出破坏miRNA对免疫作用的方法。认识到这一点催生了新的实验性治疗方法,如针对宿主miRNA的丙型肝炎治疗药物RG-101和Miravirsen。miRNA正在作为新型感染生物标志物进行研究,并被用于设计减毒疫苗,例如针对登革热病毒的疫苗。这篇综述综合了目前关于miRNA在宿主对感染反应中的知识,重点介绍了潜在的临床应用,并评估了仍需克服的挑战。