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

Front Immunol. 2020 Mar 3:11:367. doi: 10.3389/fimmu.2020.00367. eCollection 2020.

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.

Keywords: BART miRNA; BHRF miRNA; herpes virus; immune evasion; microRNAs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity / genetics
  • Alternative Splicing
  • Carcinoma / genetics
  • Carcinoma / immunology
  • Carcinoma / virology
  • Cytopathogenic Effect, Viral / genetics
  • Epithelial Cells / virology
  • Epstein-Barr Virus Infections / genetics
  • Epstein-Barr Virus Infections / immunology*
  • Gene Expression Regulation, Viral*
  • Herpesvirus 4, Human / genetics*
  • Herpesvirus 4, Human / immunology
  • Herpesvirus 4, Human / physiology
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Immune Evasion / genetics
  • Immunity, Innate / genetics
  • Immunologic Surveillance
  • Lymphoma / genetics
  • Lymphoma / immunology
  • Lymphoma / virology
  • MicroRNAs / genetics
  • MicroRNAs / immunology*
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / immunology
  • Nasopharyngeal Neoplasms / virology
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • RNA, Viral / genetics
  • RNA, Viral / immunology*
  • Viral Matrix Proteins / physiology
  • Viral Proteins / biosynthesis
  • Viral Proteins / genetics
  • Viral Proteins / immunology
  • Virus Latency / genetics
  • Virus Latency / immunology

Substances

  • BHRF1 protein, Human herpesvirus 4
  • EBV-BART10-3p microRNA
  • EBV-associated membrane antigen, Epstein-Barr virus
  • MicroRNAs
  • RNA, Viral
  • Viral Matrix Proteins
  • Viral Proteins