The Membrane Protein Of Sars-Cov Suppresses Nf-Kappa B 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 I kappa B kinase (IKK) signalsome and subsequently the nuclear factor kappa B (NF-kappa B), 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 IKK beta using a co-immunoprecipitation assay (IPA). Expression of M suppressed tumor necrosis factor alpha (TNF-alpha.) induced NF-kappa B 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-kappa B activity probably through a direct interaction with IKK beta, resulting in lower Cox-2 expression. Suppression of NF-kappa B activity and Cox-2 expression may contribute to SARS pathogenesis.