Severe Acute Respiratory Syndrome Coronavirus nsp1 Facilitates Efficient Propagation in Cells through a Specific Translational Shutoff of Host mRNA
Open Access
- 15 October 2012
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 86 (20) , 11128-11137
- https://doi.org/10.1128/jvi.01700-12
Abstract
Severe acute respiratory syndrome (SARS) coronavirus (SCoV) is an enveloped virus containing a single-stranded, positive-sense RNA genome. Nine mRNAs carrying a set of common 5′ and 3′ untranslated regions (UTR) are synthesized from the incoming viral genomic RNA in cells infected with SCoV. A nonstructural SCoV nsp1 protein causes a severe translational shutoff by binding to the 40S ribosomal subunits. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5′UTR of host mRNA. However, the mechanism by which SCoV viral proteins are efficiently produced in infected cells in which host protein synthesis is impaired by nsp1 is unknown. In this study, we investigated the role of the viral UTRs in evasion of the nsp1-mediated shutoff. Luciferase activities were significantly suppressed in cells expressing nsp1 together with the mRNA carrying a luciferase gene, while nsp1 failed to suppress luciferase activities of the mRNA flanked by the 5′UTR of SCoV. An RNA-protein binding assay and RNA decay assay revealed that nsp1 bound to stem-loop 1 (SL1) in the 5′UTR of SCoV RNA and that the specific interaction with nsp1 stabilized the mRNA carrying SL1. Furthermore, experiments using an SCoV replicon system showed that the specific interaction enhanced the SCoV replication. The specific interaction of nsp1 with SL1 is an important strategy to facilitate efficient viral gene expression in infected cells, in which nsp1 suppresses host gene expression. Our data indicate a novel mechanism of viral gene expression control by nsp1 and give new insight into understanding the pathogenesis of SARS.This publication has 41 references indexed in Scilit:
- Binding of the 5'-untranslated region of coronavirus RNA to zinc finger CCHC-type and RNA-binding motif 1 enhances viral replication and transcriptionNucleic Acids Research, 2012
- Blocking eIF4E-eIF4G Interaction as a Strategy To Impair Coronavirus ReplicationJournal of Virology, 2011
- The solution structure of coronaviral stem-loop 2 (SL2) reveals a canonical CUYG tetraloop foldFEBS Letters, 2011
- A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 proteinNature Structural & Molecular Biology, 2009
- Bovine Coronavirus Nonstructural Protein 1 (p28) Is an RNA Binding Protein That Binds Terminal Genomic cis -Replication ElementsJournal of Virology, 2009
- Structural Lability in Stem–Loop 1 Drives a 5′ UTR–3′ UTR Interaction in Coronavirus ReplicationJournal of Molecular Biology, 2008
- Severe Acute Respiratory Syndrome Coronavirus Evades Antiviral Signaling: Role of nsp1 and Rational Design of an Attenuated StrainJournal of Virology, 2007
- Putative cis -Acting Stem-Loops in the 5′ Untranslated Region of the Severe Acute Respiratory Syndrome Coronavirus Can Substitute for Their Mouse Hepatitis Virus CounterpartsJournal of Virology, 2006
- Construction of a Severe Acute Respiratory Syndrome Coronavirus Infectious cDNA Clone and a Replicon To Study Coronavirus RNA SynthesisJournal of Virology, 2006
- Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression by promoting host mRNA degradationProceedings of the National Academy of Sciences, 2006