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Nonsense-mediated mRNA decay does not restrict influenza A virus propagation

Giao Vu Quynh Tran1, Jens Kleinehr1, Hannah Franziska Preugschas1

  • 1Institute of Virology Muenster (IVM), University Hospital Muenster (UKM), Muenster, Germany.

Cellular Microbiology
|March 3, 2021
PubMed

Insights

Nonsense-mediated mRNA decay (NMD) is an antiviral process, but this study found it does not restrict negative-sense single-stranded RNA ((-)ssRNA) viruses like Influenza A virus. Inhibiting NMD did not significantly alter viral replication.

Area of Science:

  • Molecular Biology
  • Virology
  • Cellular Biology

Background:

  • Nonsense-mediated mRNA decay (NMD) degrades faulty cellular mRNA and acts as an antiviral mechanism.
  • NMD's antiviral role is established for positive-sense single-stranded RNA ((+)ssRNA) viruses, but its effect on negative-sense single-stranded RNA ((-)ssRNA) viruses is less understood.

Purpose of the Study:

  • To investigate whether NMD restricts the replication of (-)ssRNA viruses, specifically Influenza A virus (IAV) and Respiratory Syncytial Virus (RSV).
  • To determine if inhibiting key NMD factors impacts IAV and RSV replication.

Main Methods:

  • Knockdown of the central NMD factor, up-frameshift protein 1 (UPF1).
  • Pharmacological inhibition of NMD components.
  • Monitoring viral mRNA and protein levels.
  • Assessing viral replication rates for IAV and RSV.

Main Results:

  • Knockdown of UPF1 showed a slight increase in viral mRNA and protein levels for (-)ssRNA viruses.
  • No significant alteration in the overall replication of IAV or RSV was observed despite NMD inhibition.
  • These findings suggest NMD may not be a major antiviral defense against these specific (-)ssRNA viruses.

Conclusions:

  • The NMD pathway does not appear to possess significant restricting capacities against (-)ssRNA viruses like IAV and RSV.
  • Further research is needed to fully elucidate the interplay between NMD and viral replication, particularly for different viral genome types.
Keywords:
diseasesinfectionmRNA decayviral replicationviruses

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