Format

Send to

Choose Destination
Cell Host Microbe. 2017 Sep 13;22(3):377-386.e5. doi: 10.1016/j.chom.2017.08.004.

Epitranscriptomic Enhancement of Influenza A Virus Gene Expression and Replication.

Author information

1
Department of Molecular Genetics & Microbiology and Center for Virology, Duke University Medical Center, Durham, NC 27710, USA.
2
Department of Molecular Genetics & Microbiology and Center for Virology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: bryan.cullen@duke.edu.

Abstract

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.

KEYWORDS:

RNA methylation; YTHDF2; epitranscriptomics; influenza A virus; m(6)A; mRNA function; post-transcriptional regulation; viral pathogenesis

PMID:
28910636
PMCID:
PMC5615858
DOI:
10.1016/j.chom.2017.08.004
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center