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

被引：136

作者：

Balistreri, Giuseppe ^{[1
]}

Horvath, Peter ^{[2
,3
]}

Schweingruber, Christoph ^{[4
,5
]}

Zuend, David ^{[4
]}

McInerney, Gerald ^{[6
]}

Merits, Andres ^{[7
]}

Muehlemann, Oliver ^{[4
]}

Azzalin, Claus ^{[1
]}

Helenius, Ari ^{[1
]}

机构：

[1] ETH, Inst Biochem, CH-8093 Zurich, Switzerland

[2] Biol Res Ctr, Synthet & Syst Biol Unit, H-6726 Szeged, Hungary

[3] Univ Helsinki, FIMM Inst, FIN-00014 Helsinki, Finland

[4] Univ Bern, Dept Chem & Biochem, CH-3012 Bern, Switzerland

[5] Univ Bern, Grad Sch Cellular & Biomed Sci, CH-3012 Bern, Switzerland

[6] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden

[7] Univ Tartu, Inst Technol, EE-50090 Tartu, Estonia

来源：

CELL HOST & MICROBE | 2014年 / 16卷 / 03期

基金：

瑞士国家科学基金会;

关键词：

SEMLIKI-FOREST-VIRUS; TEMPERATURE-SENSITIVE MUTANTS; PLASMA-MEMBRANE; HUMAN-CELLS; UPF1; PHOSPHORYLATION; COMPLEX; SURVEILLANCE; BINDING; DEGRADATION; HELICASE;

D O I：

10.1016/j.chom.2014.08.007

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：403 / 411

页数：9

共 39 条

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