Mammalian microRNA: an important modulator of host-pathogen interactions in human viral infections.

Chet Raj Ojha,Rita Mukhopadhyay,Myosotys Rodriguez,Nazira El-Hage,Seth M. Dever

doi:10.1186/s12929-016-0292-x

Chet Raj Ojha, Rita Mukhopadhyay + Show 3 more

Open Access

https://doi.org/10.1186/s12929-016-0292-x

Copy DOI

Abstract

MicroRNAs (miRNAs), which are small non-coding RNAs expressed by almost all metazoans, have key roles in the regulation of cell differentiation, organism development and gene expression. Thousands of miRNAs regulating approximately 60 % of the total human genome have been identified. They regulate genetic expression either by direct cleavage or by translational repression of the target mRNAs recognized through partial complementary base pairing. The active and functional unit of miRNA is its complex with Argonaute proteins known as the microRNA-induced silencing complex (miRISC). De-regulated miRNA expression in the human cell may contribute to a diverse group of disorders including cancer, cardiovascular dysfunctions, liver damage, immunological dysfunction, metabolic syndromes and pathogenic infections. Current day studies have revealed that miRNAs are indeed a pivotal component of host-pathogen interactions and host immune responses toward microorganisms. miRNA is emerging as a tool for genetic study, therapeutic development and diagnosis for human pathogenic infections caused by viruses, bacteria, parasites and fungi. Many pathogens can exploit the host miRNA system for their own benefit such as surviving inside the host cell, replication, pathogenesis and bypassing some host immune barriers, while some express pathogen-encoded miRNA inside the host contributing to their replication, survival and/or latency. In this review, we discuss the role and significance of miRNA in relation to some pathogenic viruses.

Highlights

Recent advancements in genomics and proteomics have shown that out of roughly half of the human genome which is transcribed into Ribonucleic acid (RNA) transcripts, about 2 % is translated into the corresponding amino acid sequences [1]
The exciting avenue of miRNA was unraveled in 1993 by the finding that Lin-4, a heterochronic gene previously recognized for its role in regulating the temporal sequence of events involved in Caenorhabditis elegans (C. elegans) larval development to adult form, regulates the process by synthesizing a pair of small RNAs rather than coding for a protein [9]
CD4+ T-cells have been found to express some miRNAs which target messenger RNA (mRNA) of the viral genes (Fig. 2); negative regulatory factor, viral protein s(vpr), viral infectivity factor and viral protein U; and regulate host factors like Cyclin T1 protein and receptors or co-receptors needed for Human Immunodeficiency Virus (HIV) entry [73,74,75,76]

Summary

Introduction

Recent advancements in genomics and proteomics have shown that out of roughly half of the human genome which is transcribed into RNA transcripts, about 2 % is translated into the corresponding amino acid sequences [1]. HCV infection up-regulates miR-21 and miR-130a expression, both of which negatively regulate their target genes known to trigger viral replication in cells, by decreasing HCV-mediated IFN type I (IFN-I) production and disrupting the process of viral entry, respectively [61, 62]. MiRNA modulating Hepatitis B virus infection Several cellular miRNAs modulate Hepatitis B virus (HBV) replication directly by binding to its transcripts (Fig. 2) or indirectly by targeting cellular factors, genes and signaling pathways related to HBV replication and pathogenesis (Table 1) [67].

Results

Conclusion