The Interplay Between Viral-Derived miRNAs and Host Immunity During Infection.

Ashish Kumar,Richa Mishra,Himanshu Kumar,Harshad Ingle

doi:10.3389/fimmu.2019.03079

Abstract

MicroRNAs are short non-coding RNAs that play a crucial role in the regulation of gene expression during cellular processes. The host-encoded miRNAs are known to modulate the antiviral defense during viral infection. In the last decade, multiple DNA and RNA viruses have been shown to produce miRNAs known as viral miRNAs (v-miRNAs) so as to evade the host immune response. In this review, we highlight the origin and biogenesis of viral miRNAs during the viral lifecycle. We also explore the role of viral miRNAs in immune evasion and hence in maintaining chronic infection and disease. Finally, we offer insights into the underexplored role of viral miRNAs as potential targets for developing therapeutics for treating complex viral diseases.

Highlights

Until the twenty first century, it was assumed that more than 95% of the eukaryotic genome is “junk” DNA; the advent of next-generation sequencing and high throughput functional screening has highlighted the regulatory functions of the non-coding genome
MicroRNAs are small RNA molecules (18–22 nt) that play a crucial role in the regulation of gene expression by binding to the 3′ untranslated region (3′UTR) of target messenger RNAs [5,6,7]. miRNA-mRNA interaction results in mRNA degradation or translation inhibition, thereby resulting in reduced gene expression, thereby modulating the biological function [8, 9]
We summarize the miRNA-like non-coding RNAs encoded by DNA and RNA viruses and their roles in the evasion of host immunity

Summary

INTRODUCTION

Until the twenty first century, it was assumed that more than 95% of the eukaryotic genome is “junk” DNA; the advent of next-generation sequencing and high throughput functional screening has highlighted the regulatory functions of the non-coding genome. The role of miRNAs in the development of immune responses in viral infections has been a subject of immense research interest. MicroRNAs are small RNA molecules (18–22 nt) that play a crucial role in the regulation of gene expression by binding to the 3′ untranslated region (3′UTR) of target messenger RNAs (mRNAs) [5,6,7]. In addition to the hundreds of eukaryotic cellular miRNAs, miRNAs of viral origin ( known as v-miRNAs) have been discovered that can function as post-transcriptional gene regulators to host as well as viral genes [12, 13]. We summarize the miRNA-like non-coding RNAs encoded by DNA and RNA viruses and their roles in the evasion of host immunity. We discuss the possible role of these v-miRNAs as potential targets for developing therapeutics for the treatment of viral diseases

DISCOVERY AND ORIGIN OF VIRAL miRNAs

Influenza Virus

Ebola Virus

Targeting the Viral Gene Expression

Targeting the Host Cellular Genes

Viral oncogenesis in NPC and immune evasion

Lytic reactivation Latency establishment

Cell cycle regulation and tumor suppression

Multiple cellular targets

Regulate HBc protein and pgRNA levels to alter viral replication

Enhances promoter activity and viral infection

Findings