The Clinical Application of MicroRNAs in Infectious Disease

Abstract

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.

Identification of genes and regulators that are shared across T cell associated diseases

“…microRNA profiles in cells isolated from patients suffering from viral, bacterial or fungal infections differed from healthy controls [60]. This tendency has been also shown in vitro infected cells [60].…”

“…Those are short (∼22nt long) noncoding RNAs that post-transcriptionally negatively regulate gene expression. It is estimated that microRNAs regulate around 60% of protein coding genes [60]. Canonically, microRNAs fine-tune mRNA expression by binding to the transcripts 3'UTR region and inducing either mRNA cleavage or causing inhibition of translation [60].…”

“…It is estimated that microRNAs regulate around 60% of protein coding genes [60]. Canonically, microRNAs fine-tune mRNA expression by binding to the transcripts 3'UTR region and inducing either mRNA cleavage or causing inhibition of translation [60]. For the interaction to be present it is commonly accepted that the miR 'seed' region has to be perfectly or nearly perfectly complementary to the mRNA sequence [60,61].…”

“…Canonically, microRNAs fine-tune mRNA expression by binding to the transcripts 3'UTR region and inducing either mRNA cleavage or causing inhibition of translation [60]. For the interaction to be present it is commonly accepted that the miR 'seed' region has to be perfectly or nearly perfectly complementary to the mRNA sequence [60,61]. Usually 'seed' denotes nucleotides at the 2 nd to 7 th position at the 5' end of the microRNA [61] and has been shown to be most conserved among the miR sequence [61].…”

“…Furthermore, miRs are thought to be key mediators in the host response to infections, they are involved in innate and adaptive immune pathways [60]. Since miRs seem to play an important role in mediating host response to infection, their deregulation may in turn lead to susceptibility towards disease [60].…”