Epitranscriptomic Enhancement of Influenza A Virus Gene Expression and Replication.

Published

Journal Article

Many viral RNAs are modified by methylation of the N6 position of adenosine (m6A). m6A is thought to regulate RNA splicing, stability, translation, and secondary structure. Influenza A virus (IAV) expresses m6A-modified RNAs, but the effects of m6A on this segmented RNA virus remain unclear. We demonstrate that global inhibition of m6A addition inhibits IAV gene expression and replication. In contrast, overexpression of the cellular m6A "reader" protein YTHDF2 increases IAV gene expression and replication. To address whether m6A residues modulate IAV RNA function in cis, we mapped m6A residues on the IAV plus (mRNA) and minus (vRNA) strands and used synonymous mutations to ablate m6A on both strands of the hemagglutinin (HA) segment. These mutations inhibited HA mRNA and protein expression while leaving other IAV mRNAs and proteins unaffected, and they also resulted in reduced IAV pathogenicity in mice. Thus, m6A residues in IAV transcripts enhance viral gene expression.

Full Text

Duke Authors

Cited Authors

  • Courtney, DG; Kennedy, EM; Dumm, RE; Bogerd, HP; Tsai, K; Heaton, NS; Cullen, BR

Published Date

  • September 2017

Published In

Volume / Issue

  • 22 / 3

Start / End Page

  • 377 - 386.e5

PubMed ID

  • 28910636

Pubmed Central ID

  • 28910636

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

International Standard Serial Number (ISSN)

  • 1931-3128

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2017.08.004

Language

  • eng