Article
Inhibition of interferon induction by the SARS-associated coronavirus
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Published: | May 26, 2004 |
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We and others have previously shown that replication of SARS-CoV in cell culture can be efficiently inhibited by exogenously added interferon- (IFN-) beta ([Ref. 1], [Ref. 2]). Here, we investigated whether SARS-CoV is able to circumvent the induction of IFN to allow better growth in vivo. In cells infected with SARS-CoV, no endogenous IFN-beta transcripts were detected and no activation of the IFN-beta promoter occurred. To further analyze this block of IFN induction, we focused on IRF-3 which is the key transcription factor for the IFN-beta promoter. In uninfected cells, IRF-3 is present in the cytoplasm where it becomes activated by virus infection. Normally, IRF-3 then homodimerizes, translocates to the nucleus and transactivates the IFN-beta promoter. Nuclear translocation of IRF-3 was observed in SARS-CoV-infected cells. Homodimerization of IRF-3, however was not detectable. As a consequence, IRF-3 failed to bind to CBP, the essential coactivator of IFN transcription. Our data indicate that SARS-CoV circumvents IFN induction by inhibiting the homodimerization of IRF-3. Therefore, IRF-3 is unable to recruit the cofactor CBP, resulting in a block of IFN-beta transcription.