The membrane protein of SARS-CoV suppresses NF-kappaB activation.
Severe acute respiratory syndrome coronavirus (SARS-CoV) infects many organs, such as lung, liver, and immune organs and causes life-threatening atypical pneumonia, SARS causes high morbidity and mortality rates. The molecular mechanism of SARS pathogenesis remains elusive. Inflammatory stimuli can activate IkappaB kinase (IKK) signalsome and subsequently the nuclear factor kappa B (NF-kappaB), which influences gene expression of cyclooxygenase-2 (Cox-2) along with other transcription factors. In this work, we found that the membrane (M) protein of SARS-CoV physically interacted with IKKbeta using a co-immunoprecipitation assay (IPA). Expression of M suppressed tumor necrosis factor alpha (TNF-alpha) induced NF-kappaB activation using a luciferase reporter assay. Further investigation showed M protein suppressed Cox-2 expression using a luciferase reporter gene assay, RT-PCR and Western blot analysis. The carboxyl terminal of M protein was sufficient for the M protein function. Together, these results indicate that SARS-CoV M suppresses NF-kappaB activity probably through a direct interaction with IKKbeta, resulting in lower Cox-2 expression. Suppression of NF-kappaB activity and Cox-2 expression may contribute to SARS pathogenesis.
Fang
Xiaonan
X
State Key Laboratory of Virology, College of Life Science, Wuhan University, Wuhan, Hubei, China.
Gao
Jinrong
J
Zheng
Hong
H
Li
Baozong
B
Kong
Lingbao
L
Zhang
Yijuan
Y
Wang
Wei
W
Zeng
Yingchun
Y
Ye
Linbai
L
D000818:Animals; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D000086862:Coronavirus M Proteins; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry / Q000378:metabolism* / Q000472:pathogenicity; D045169:Severe Acute Respiratory Syndrome / Q000378:metabolism* / Q000821:virology; D015398:Signal Transduction; D014709:Vero Cells; D014763:Viral Matrix Proteins / Q000502:physiology*; D014774:Virulence
D000086862:Coronavirus M Proteins; D020672:I-kappa B Proteins; C000706237:M protein, SARS-CoV; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014763:Viral Matrix Proteins; D000072000:NF-KappaB Inhibitor alpha; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D051550:I-kappa B Kinase
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