A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein

• Published in: Nature structural & molecular biology Vol. 16; no. 11; pp. 1134 - 1140
• Main Authors: Kamitani, Wataru, Huang, Cheng, Narayanan, Krishna, Lokugamage, Kumari G, Makino, Shinji
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2009; Nature Publishing Group
• Subjects: Biochemistry; Biological Microscopy; Biological response modifiers; Biomedical and Life Sciences; Cell Line; Coronaviruses; COVID-19; Cricket (Sport); Degradation; Encephalomyocarditis virus; Gene expression; Genes; Genetic aspects; Gryllidae; Health aspects; Hepatitis; Hepatitis C; Humans; Immunoprecipitation; Interferon; Internal ribosome entry site; Life Sciences; Luciferases, Renilla - genetics; Luciferases, Renilla - metabolism; Membrane Biology; Messenger RNA; Molecular biology; Novels; NSP1 protein; Paralysis; Physiological aspects; Post-transcription; Protein Binding; Protein biosynthesis; Protein Biosynthesis - drug effects; Protein Biosynthesis - genetics; Protein Structure; Protein synthesis; Proteins; Ribonucleic acid; Ribosomes - metabolism; RNA; RNA modification; RNA Stability; RNA-Dependent RNA Polymerase - genetics; RNA-Dependent RNA Polymerase - metabolism; RNA-Dependent RNA Polymerase - pharmacology; RNA-Dependent RNA Polymerase - physiology; SARS coronavirus; Severe acute respiratory syndrome; Transcription (Genetics); Translation; Translation (Genetics); Viral diseases; Viral Nonstructural Proteins - genetics; Viral Nonstructural Proteins - metabolism; Viral Nonstructural Proteins - pharmacology; Viral Nonstructural Proteins - physiology; Viral proteins; Viruses; United States
• ISSN: 1545-9993; 1545-9985
• DOI: 10.1038/nsmb.1680

The SARS coronavirus protein nsp1 can suppress host gene expression at a post-transcriptional level, with previous work showing a reduction in mRNA abundance. Now a direct effect on protein synthesis is revealed, as nsp1 modifies transcripts and also inactivates the 40S ribosomal subunit. Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression, including type I interferon production, by promoting host mRNA degradation and inhibiting host translation, in infected cells. We present evidence that nsp1 uses a novel, two-pronged strategy to inhibit host translation and gene expression. Nsp1 bound to the 40S ribosomal subunit and inactivated the translational activity of the 40S subunits. Furthermore, the nsp1–40S ribosome complex induced the modification of the 5′ region of capped mRNA template and rendered the template RNA translationally incompetent. Nsp1 also induced RNA cleavage in templates carrying the internal ribosome entry site (IRES) from encephalomyocarditis virus, but not in those carrying IRES elements from hepatitis C or cricket paralysis viruses, demonstrating that the nsp1-induced RNA modification was template-dependent. We speculate that the mRNAs that underwent the nsp1-mediated modification are marked for rapid turnover by the host RNA degradation machinery.