Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression by promoting host mRNA degradation

Wataru Kamitani, Krishna Narayanan, Cheng Huang, Kumari Lokugamage, Tetsuro Ikegami, Naoto Ito, Hideyuki Kubo, Shinji Makino

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

Severe acute respiratory syndrome (SARS) coronavirus (SCoV) causes a recently emerged human disease associated with pneumonia. The 5′ end two-thirds of the single-stranded positive-sense viral genomic RNA, gene 1, encodes 16 mature proteins. Expression of nsp1, the most N-terminal gene 1 protein, prevented Sendai virus-induced endogenous IFN-β mRNA accumulation without inhibiting dimerization of IFN regulatory factor 3, a protein that is essential for activation of the IFN-β promoter. Furthermore, nsp1 expression promoted degradation of expressed RNA transcripts and host endogenous mRNAs, leading to a strong host protein synthesis inhibition. SCoV replication also promoted degradation of expressed RNA transcripts and host mRNAs, suggesting that nsp1 exerted its mRNA destabilization function in infected cells. In contrast to nsp1-induced mRNA destablization, no degradation of the 28S and 18S rRNAs occurred in either nsp1-expressing cells or SCoV-infected cells. These data suggested that, in infected cells, nsp1 promotes host mRNA degradation and thereby suppresses host gene expression, including proteins involved in host innate immune functions. SCoV nsp1-mediated promotion of host mRNA degradation may play an important role in SCoV pathogenesis.

Original languageEnglish (US)
Pages (from-to)12885-12890
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number34
DOIs
StatePublished - Aug 22 2006

Fingerprint

Severe Acute Respiratory Syndrome
Coronavirus
SARS Virus
RNA Stability
Gene Expression
Messenger RNA
Proteins
Interferon Regulatory Factor-3
Sendai virus
Viral RNA
Dimerization
Pneumonia
Genes

Keywords

  • Innate immunity
  • mRNA stability
  • SARS
  • Translation inhibition
  • Virus virulence

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression by promoting host mRNA degradation. / Kamitani, Wataru; Narayanan, Krishna; Huang, Cheng; Lokugamage, Kumari; Ikegami, Tetsuro; Ito, Naoto; Kubo, Hideyuki; Makino, Shinji.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 34, 22.08.2006, p. 12885-12890.

Research output: Contribution to journalArticle

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