IkappaB-mediated inhibition of virus-induced beta interferon transcription.

Abstract

We have examined the consequences of overexpression of the IkappaBalpha and IkappaBbeta inhibitory proteins on the regulation of NF-kappaB-dependent beta interferon (IFN-beta) gene transcription in human cells after Sendai virus infection. In transient coexpression studies or in cell lines engineered to express different forms of IkappaB under tetracycline-inducible control, the IFN-beta promoter (-281 to +19) linked to the chloramphenicol acetyltransferase reporter gene was differentially inhibited in response to virus infection. IkappaBalpha exhibited a strong inhibitory effect on virus-induced IFN-beta expression, whereas IkappaBbeta exerted an inhibitory effect only at a high concentration. Despite activation of the IkappaB kinase complex by Sendai virus infection, overexpression of the double-point-mutated (S32A/S36A) dominant repressors of IkappaBalpha (TD-IkappaBalpha) completely blocked IFN-beta gene activation by Sendai virus. Endogenous IFN-beta RNA production was also inhibited in Tet-inducible TD-IkappaBalpha-expressing cells. Inhibition of IFN-beta expression directly correlated with a reduction in the binding of NF-kappaB (p50-RelA) complex to PRDII after Sendai virus infection in IkappaBalpha-expressing cells, whereas IFN-beta expression and NF-kappaB binding were only slightly reduced in IkappaBbeta-expressing cells. These experiments demonstrate a major role for IkappaBalpha in the regulation of NF-kappaB-induced IFN-beta gene activation and a minor role for IkappaBbeta in the activation process.

• Authors: M Algarté, H Nguyen, C Heylbroeck, R Lin, J Hiscott
• Journal: Journal of virology (J Virol) Vol. 73 Issue 4 Pg. 2694-702 (Apr 1999) ISSN: 0022-538X [Print] United States
• PMID: 10074115 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• I-kappa B Proteins
• RNA, Messenger
• Interferon-beta

Topics

• Amino Acid Sequence
• Cell Line
• DNA-Binding Proteins (biosynthesis, genetics)
• Gene Expression Regulation, Viral
• Humans
• I-kappa B Proteins
• Interferon-beta (biosynthesis, genetics)
• Molecular Sequence Data
• RNA, Messenger (analysis, genetics)
• Respirovirus
• Respirovirus Infections (genetics)
• Transcription, Genetic
• Transcriptional Activation