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

doi:10.1073/pnas.0603144103

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

*Departments of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1019; and
^†Laboratory of Zoonotic Diseases, Division of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan

Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved June 30, 2006 (received for review April 18, 2006)

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.

Footnotes

^‡To whom correspondence should be addressed. E-mail: shmakino{at}utmb.edu
Author contributions: W.K. and S.M. designed research; W.K., K.N., C.H., K.L., T.I., N.I., and H.K. performed research; C.H., K.L., T.I., and H.K. contributed new reagents/analytic tools; W.K. and S.M. analyzed data; and W.K. and S.M. wrote the paper.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

ACE,

angiotensin converting enzyme;

actD,

actinomycin D;

CAT,

chloramphenicol acetyltransferase;

HSV,

herpes simplex virus;

IRF,

IFN regulatory factor;

Luc,

luciferase;

moi,

multiplicity of infection;

p.i.,

postinfection;

RVFV,

Rift Valley fever virus;

SCoV,

severe acute respiratory syndrome coronavirus;

SeV,

Sendai virus;

vhs,

virion host shutoff