Alphaherpesvirus-mediated remodeling of the cellular transcriptome results in depletion of m6A-containing transcripts. Academic Article uri icon

Overview

abstract

  • The mechanisms by which viruses regulate host mRNAs during infection are still poorly understood. Several host transcripts that encode proteins that contribute to the anti-viral response contain the N6-methyladenosine nucleotide (m6A). In this study, we investigated if and how viruses from different (sub) families specifically affect m6A-containing host transcripts. Systematic analysis of host transcriptomes after infection with diverse types of viruses showed that m6A-methylated transcripts are selectively downregulated during infection with Sendai virus, African swine fever virus and the alphaherpesviruses herpes simplex virus 1 (HSV-1) and pseudorabies virus (PRV). Focusing on PRV and HSV-1, we found that downregulation of m6A-methylated transcripts depends on the YTHDF family of m6A-binding proteins, and correlates with localization of these proteins to enlarged P-bodies. Knockdown of YTHDF proteins in primary cells reduced PRV protein expression and increased expression of antiviral interferon-stimulated genes, suggesting that virus-induced depletion of host m6A-containing transcripts constitutes an immune evasion strategy.

publication date

  • July 10, 2023

Identity

PubMed Central ID

  • PMC10415716

Scopus Document Identifier

  • 85166180871

Digital Object Identifier (DOI)

  • 10.1016/j.isci.2023.107310

PubMed ID

  • 37575180

Additional Document Info

volume

  • 26

issue

  • 8