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. 2007 Aug 17;79(10):1431–1439. doi: 10.1002/jmv.20953

The membrane protein of SARS‐CoV suppresses NF‐κB activation

Xiaonan Fang 1, Jinrong Gao 1,2, Hong Zheng 1, Baozong Li 1, Lingbao Kong 1, Yijuan Zhang 1, Wei Wang 1, Yingchun Zeng 1, Linbai Ye 1,✉
PMCID: PMC7166727  PMID: 17705188

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 IκB kinase (IKK) signalsome and subsequently the nuclear factor kappa B (NF‐κB), 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 IKKβ using a co‐immunoprecipitation assay (IPA). Expression of M suppressed tumor necrosis factor alpha (TNF‐α) induced NF‐κB 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‐κB activity probably through a direct interaction with IKKβ, resulting in lower Cox‐2 expression. Suppression of NF‐κB activity and Cox‐2 expression may contribute to SARS pathogenesis. J. Med. Virol. 79:1431–1439, 2007. © Wiley‐Liss, Inc.

Keywords: SARS‐CoV, membrane protein, NF‐κB, Cox‐2, IKKβ

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