Alphaherpesvirus-mediated Remodeling of the Cellular Transcriptome Results in Depletion of M6A-containing Transcripts

Overview

Journal iScience

Publisher Cell Press

Date 2023 Aug 14

PMID 37575180

Authors

Robert J J Jansens

Anthony Olarerin-George

Ruth Verhamme

Aashiq Mirza

Samie Jaffrey

Herman W Favoreel

Affiliations

Soon will be listed here.

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.

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