The host nonsense-mediated mRNA decay pathway restricts Mammalian RNA virus replication

Cell Host Microbe. 2014 Sep 10;16(3):403-11. doi: 10.1016/j.chom.2014.08.007.


In addition to classically defined immune mechanisms, cell-intrinsic processes can restrict virus infection and have shaped virus evolution. The details of this virus-host interaction are still emerging. Following a genome-wide siRNA screen for host factors affecting replication of Semliki Forest virus (SFV), a positive-strand RNA (+RNA) virus, we found that depletion of nonsense-mediated mRNA decay (NMD) pathway components Upf1, Smg5, and Smg7 led to increased levels of viral proteins and RNA and higher titers of released virus. The inhibitory effect of NMD was stronger when virus replication efficiency was impaired by mutations or deletions in the replicase proteins. Consequently, depletion of NMD components resulted in a more than 20-fold increase in production of these attenuated viruses. These findings indicate that a cellular mRNA quality control mechanism serves as an intrinsic barrier to the translation of early viral proteins and the amplification of +RNA viruses in animal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphavirus Infections / genetics
  • Alphavirus Infections / metabolism
  • Alphavirus Infections / virology*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Host-Pathogen Interactions
  • Humans
  • Nonsense Mediated mRNA Decay*
  • RNA Helicases
  • Semliki forest virus / genetics
  • Semliki forest virus / physiology*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virus Release
  • Virus Replication*


  • Carrier Proteins
  • SMG5 protein, human
  • SMG7 protein, human
  • Trans-Activators
  • Viral Proteins
  • RNA Helicases
  • UPF1 protein, human