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

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

Giuseppe Balistreri  1 , Peter Horvath  2 , Christoph Schweingruber  3 , David Zünd  4 , Gerald McInerney  5 , Andres Merits  6 , Oliver Mühlemann  4 , Claus Azzalin  7 , Ari Helenius  7
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Free article

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

Giuseppe Balistreri et al. Cell Host Microbe. .
Free article

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.

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  • NMD: nonsense-mediated defense.
    Wachter A, Hartmann L. Wachter A, et al. Cell Host Microbe. 2014 Sep 10;16(3):273-5. doi: 10.1016/j.chom.2014.08.015. Cell Host Microbe. 2014. PMID: 25211070

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