title: The host nonsense-mediated mRNA decay pathway restricts Mammalian RNA virus replication.
abstract: 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.
authors.affiliation: Institute of Biochemistry, ETH Zürich, 8093 Zürich, Switzerland. Electronic address: giuseppe.balistreri@helsinki.fi.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Balistreri
authors.affiliation: Synthetic and System Biology Unit, Biological Research Center, 6726 Szeged, Hungary; FIMM Institute, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Peter
authors.initials: P
authors.lastname: Horvath
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, 3012 Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schweingruber
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, 3012 Bern, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Zünd
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17177 Stockholm, Sweden.
authors.forename: Gerald
authors.initials: G
authors.lastname: McInerney
authors.affiliation: Institute of Technology, University of Tartu, 50090 Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Merits
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, 3012 Bern, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Mühlemann
authors.affiliation: Institute of Biochemistry, ETH Zürich, 8093 Zürich, Switzerland.
authors.forename: Claus
authors.initials: C
authors.lastname: Azzalin
authors.affiliation: Institute of Biochemistry, ETH Zürich, 8093 Zürich, Switzerland.
authors.forename: Ari
authors.initials: A
authors.lastname: Helenius
mesh_terms: D018354:Alphavirus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D059365:Nonsense Mediated mRNA Decay; D020365:RNA Helicases; D012672:Semliki forest virus / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D057074:Virus Release; D014779:Virus Replication
chemical_list: D002352:Carrier Proteins; C515801:SMG5 protein, human; C494578:SMG7 protein, human; D015534:Trans-Activators; D014764:Viral Proteins; D020365:RNA Helicases; C101828:UPF1 protein, human