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Role of microRNAs in antiviral responses to dengue infection
Journal of Biomedical Science ( IF 11.0 ) Pub Date : 2020-01-03 , DOI: 10.1186/s12929-019-0614-x
Rui Rui Wong , Noraini Abd-Aziz , Sarah Affendi , Chit Laa Poh

Dengue virus (DENV) is the etiological agent of dengue fever. Severe dengue could be fatal and there is currently no effective antiviral agent or vaccine. The only licensed vaccine, Dengvaxia, has low efficacy against serotypes 1 and 2. Cellular miRNAs are post-transcriptional regulators that could play a role in direct regulation of viral genes. Host miRNA expressions could either promote or repress viral replications. Induction of some cellular miRNAs could help the virus to evade the host immune response by suppressing the IFN-α/β signaling pathway while others could upregulate IFN-α/β production and inhibit the viral infection. Understanding miRNA expressions and functions during dengue infections would provide insights into the development of miRNA-based therapeutics which could be strategized to act either as miRNA antagonists or miRNA mimics. The known mechanisms of how miRNAs impact DENV replication are diverse. They could suppress DENV multiplication by directly binding to the viral genome, resulting in translational repression. Other miRNA actions include modulation of host factors. In addition, miRNAs that could modulate immunopathogenesis are discussed. Major hurdles lie in the development of chemical modifications and delivery systems for in vivo delivery. Nevertheless, advancement in miRNA formulations and delivery systems hold great promise for the therapeutic potential of miRNA-based therapy, as supported by Miravirsen for treatment of Hepatitis C infection which has successfully completed phase II clinical trial.

中文翻译:

microRNA在对登革热感染的抗病毒应答中的作用

登革热病毒(DENV)是登革热的病原体。严重的登革热可能致命,目前还没有有效的抗病毒剂或疫苗。唯一获得许可的疫苗Dengvaxia对血清型1和2具有较低的功效。细胞miRNA是转录后调节剂,可在病毒基因的直接调节中发挥作用。宿主miRNA表达可以促进或抑制病毒复制。某些细胞miRNA的诱导可以通过抑制IFN-α/β信号通路来帮助病毒逃避宿主的免疫反应,而另一些则可以上调IFN-α/β的产生并抑制病毒感染。了解登革热感染期间miRNA的表达和功能将为基于miRNA的疗法的发展提供见解,该疗法可被策略化为充当miRNA拮抗剂或miRNA模拟物。miRNA如何影响DENV复制的已知机制多种多样。他们可以通过直接结合病毒基因组来抑制DENV繁殖,从而导致翻译抑制。其他miRNA作用包括调节宿主因子。此外,讨论了可以调节免疫发病机制的miRNA。主要障碍在于体内递送的化学修饰和递送系统的开发。不过,miRNA制剂和递送系统的进步对基于miRNA的治疗方法的治疗潜力具有广阔的前景,
更新日期:2020-04-07
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