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RNA m6 A methylation regulates virus-host interaction and EBNA2 expression during Epstein-Barr virus infection

Xiang Zheng1,2,3,4, Jia Wang1,2,4,5, Xiaoyue Zhang2,4

  • 1Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.

Immunity, Inflammation and Disease
|January 12, 2021
PubMed
Abstract

Insights

Epstein-Barr virus (EBV) infection alters N-methyladenosine (m6A) RNA modifications in both viral and host cells. These m6A changes are crucial for the early stages of EBV infection and virus-host interactions.

Area of Science:

  • Virology
  • Molecular Biology
  • Epigenetics

Background:

  • N-methyladenosine (m6A) is the most abundant mRNA modification, regulating gene expression.
  • m6A modifications are dynamic and mediated by writers, erasers, and readers.
  • The role of m6A in viral infections, particularly during Epstein-Barr virus (EBV) de novo infection, remains largely unexplored.

Purpose of the Study:

  • To investigate the viral and cellular m6A epitranscriptomes during the pre-latent phase of de novo EBV infection.
  • To elucidate the impact of m6A modifications on EBV-host interactions.

Main Methods:

  • Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and MeRIP-RT-qPCR were employed to identify m6A-modified transcripts.
  • RNA immunoprecipitation (RIP) assays confirmed the binding of EBNA2 and m6A readers.
  • Quantitative reverse-transcription polymerase chain reaction (RT-qPCR) and Western blot analyses assessed gene expression changes.

Main Results:

  • EBV infection led to significant m6A modifications in viral transcripts EBNA2 and BHRF1.
  • Knockdown of METTL3, an m6A writer, reduced EBNA2 expression.
  • EBV infection altered m6A distribution in host transcripts, with new modifications in 3' UTRs and lost modifications in coding regions.

Conclusions:

  • m6A modification plays a critical role in the early stages of de novo EBV infection.
  • EBV infection dynamically remodels the host epitranscriptome, influencing virus-host interactions.
Keywords:
BHRF1EBNA2Epstein-Barr virusMETTL3RNA m6A methylation

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