Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression by promoting host mRNA degradation.
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-beta mRNA accumulation without inhibiting dimerization of IFN regulatory factor 3, a protein that is essential for activation of the IFN-beta 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.
Kamitani
Wataru
W
Department of Microbiology, University of Texas Medical Branch, Galveston, TX 77555-1019, USA.
Narayanan
Krishna
K
Huang
Cheng
C
Lokugamage
Kumari
K
Ikegami
Tetsuro
T
Ito
Naoto
N
Kubo
Hideyuki
H
Makino
Shinji
S
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D019281:Dimerization; D015870:Gene Expression; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D012333:RNA, Messenger; D014764:Viral Proteins; D016899:Interferon-beta