Severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type I interferon, in infected cells

Krishna Narayanan, Cheng Huang, Kumari Lokugamage, Wataru Kamitani, Tetsuro Ikegami, Chien-Te Tseng, Shinji Makino

Research output: Contribution to journalArticle

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Abstract

The severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1 protein has unique biological functions that have not been described in the viral proteins of any RNA viruses; expressed SARS-CoV nsp1 protein has been found to suppress host gene expression by promoting host mRNA degradation and inhibiting translation. We generated an nsp1 mutant (nsp1-mt) that neither promoted host mRNA degradation nor suppressed host protein synthesis in expressing cells. Both a SARS-CoV mutant virus, encoding the nsp1-mt protein (SARS-CoV-mt), and a wild-type virus (SARS-CoV-WT) replicated efficiently and exhibited similar one-step growth kinetics in susceptible cells. Both viruses accumulated similar amounts of virus-specific mRNAs and nsp1 protein in infected cells, whereas the amounts of endogenous host mRNAs were clearly higher in SARS-CoV-mt-infected cells than in SARS-CoV-WT-infected cells, in both the presence and absence of actinomycin D. Further, SARS-CoV-WT replication strongly inhibited host protein synthesis, whereas host protein synthesis inhibition in SARS-CoV-mt-infected cells was not as efficient as in SARS-CoV-WT-infected cells. These data revealed that nsp1 indeed promoted host mRNA degradation and contributed to host protein translation inhibition in infected cells. Notably, SARS-CoV-mt infection, but not SARS-CoV-WT infection, induced high levels of beta interferon (IFN) mRNA accumulation and high titers of type I IFN production. These data demonstrated that SARS-CoV nsp1 suppressed host innate immune functions, including type I IFN expression, in infected cells and suggested that SARS-CoV nsp1 most probably plays a critical role in SARS-CoV virulence.

Original languageEnglish (US)
Pages (from-to)4471-4479
Number of pages9
JournalJournal of Virology
Volume82
Issue number9
DOIs
StatePublished - May 2008

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Severe Acute Respiratory Syndrome
Interferon Type I
Coronavirus
interferons
Gene Expression
gene expression
cells
RNA Stability
Coronavirus Infections
Viruses
viruses
Proteins
protein synthesis
proteins
Severe acute respiratory syndrome coronavirus
mutants
Messenger RNA
translation (genetics)
degradation
interferon-beta

ASJC Scopus subject areas

  • Immunology

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Severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type I interferon, in infected cells. / Narayanan, Krishna; Huang, Cheng; Lokugamage, Kumari; Kamitani, Wataru; Ikegami, Tetsuro; Tseng, Chien-Te; Makino, Shinji.

In: Journal of Virology, Vol. 82, No. 9, 05.2008, p. 4471-4479.

Research output: Contribution to journalArticle

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