The Host Nonsense-Mediated mRNA Decay Pathway Restricts Mammalian RNA Virus Replication

Balistreri, Giuseppe; Horvath, Peter; Schweingruber, Christoph; Zünd, David; McInerney, Gerald; Merits, Andres; Mühlemann, Oliver; Azzalin, Claus; Helenius, Ari (2014). The Host Nonsense-Mediated mRNA Decay Pathway Restricts Mammalian RNA Virus Replication. Cell host & microbe, 16(3), pp. 403-411. Cell Press 10.1016/j.chom.2014.08.007

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry

UniBE Contributor:

Schweingruber, Christoph; Zünd, David and Mühlemann, Oliver

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

1931-3128

Publisher:

Cell Press

Language:

English

Submitter:

Christina Schüpbach

Date Deposited:

02 Oct 2014 13:32

Last Modified:

08 Dec 2014 13:58

Publisher DOI:

10.1016/j.chom.2014.08.007

BORIS DOI:

10.7892/boris.58739

URI:

https://boris.unibe.ch/id/eprint/58739

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