title: The membrane protein of SARS-CoV suppresses NF-kappaB activation.
abstract: 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.
authors: State Key Laboratory of Virology, College of Life Science, Wuhan University, Wuhan, Hubei, China.
authors: Xiaonan
authors: X
authors: Fang
authors: Jinrong
authors: J
authors: Gao
authors: Hong
authors: H
authors: Zheng
authors: Baozong
authors: B
authors: Li
authors: Lingbao
authors: L
authors: Kong
authors: Yijuan
authors: Y
authors: Zhang
authors: Wei
authors: W
authors: Wang
authors: Yingchun
authors: Y
authors: Zeng
authors: Linbai
authors: L
authors: Ye
mesh_terms: 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
chemical_list: 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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