Role of Viral and Host microRNAs in Immune Regulation of Epstein-Barr Virus-Associated Diseases.

Hisashi Iizasa,Yuichi Kanehiro,Hyoji Kim,Andy Visi Kartika,Hironori Yoshiyama

doi:10.3389/fimmu.2020.00367

Abstract

Epstein-Barr virus (EBV) is an oncogenic human herpes virus that was discovered in 1964. Viral non-coding RNAs, such as BamHI-A rightward fragment-derived microRNAs (BART miRNAs) or BamHI-H rightward fragment 1-derived miRNAs (BHRF1 miRNA) in EBV-infected cells have been recently reported. Host miRNAs are also upregulated upon EBV infection. Viral and host miRNAs are important in maintaining viral infection and evasion of host immunity. Although miRNAs in EBV-infected cells often promote cell proliferation by targeting apoptosis or cell cycle, this review focuses on the regulation of the recognition of the host immune system. This review firstly describes the location and organization of two clusters of viral miRNAs, then describes evasion from host immune surveillance systems by modulating viral gene expression or inhibiting innate and acquired immunity by viral miRNAs as well as host miRNAs. Another topic is the enigmatic depletion of viral miRNAs in several types of EBV-infected tumor cells. Finally, this review introduces the strong correlation of nasopharyngeal cancer cases with a newly identified single nucleotide polymorphism that enhances BART miRNA promoter activity.

Highlights

Epstein-Barr virus (EBV) is a double-stranded DNA virus that belongs to the Gammaherpesvirus subfamily and was discovered in a Burkitt’s lymphoma (BL) cell [1]
Following a primary infection in B lymphocytes or epithelial cells, EBV establishes a chronic infection known as latent infection
The B cell receptor (BCR) that mediates adaptive immunity as well as lytic infection in EBV-infected B lymphocytes is inhibited by miR-BamH I-H right fragment 1 (BHRF1)-2-5p and miR-BART2-5p [34]. miR-BART185p targets mitogen-activated protein kinase kinase kinase 2 (MAP3K2) that is a downstream effector in BCR signaling [28]

Summary

Introduction

Epstein-Barr virus (EBV) is a double-stranded DNA virus that belongs to the Gammaherpesvirus subfamily and was discovered in a Burkitt’s lymphoma (BL) cell [1]. A small subset of viral genes and microRNAs (miRNAs) expressed during the latent infection maintain viral episomes and stimulate host cell proliferation. EBV propagates viral genomes together with host cells during latent infection. Viral miRNAs suppress target genes in the EBV and host genomes to maintain latent EBV infection, evade the host immune surveillance system, and promote tumorigenic growth of infected cells among other functions [10].

Results

Conclusion