1. ¹Laboratory of Viral Oncology, UPR CNRS 9045, Institut André Lwoff, Villejuif, France
2. ²Sezione di Chimica Biologica, Dipartimento di scienze morfologico-biomediche, Università degli Studi di Verona, Verona, Italy
3. ³Laboratory of Virology, Université René Descartes, Hopital Cochin-Saint Vincent de Paul, Paris, France

Correspondence: Dr C Lallemand, Laboratory of Viral Oncology, UPR CNRS 9045, 7, rue guy moquet, Institut André Lwoff, Villejuif 94801, France. E-mail: lalleman@vjf.cnrs.fr

Received 10 January 2006; Revised 26 May 2006; Accepted 5 June 2006; Published online 10 July 2006.

Abstract

To characterize the mechanisms underlying apoptosis induced by viral infection, transcriptional activation of genes encoding members of the 'BH3-only' family of proteins was analysed during the course of virus infection. Among these genes, only NOXA is transcriptionally activated by vesicular stomatitis virus (VSV), sendai virus (SV), measles virus, herpes simplex virus, or dsRNA and required for efficient apoptosis of cells. Transcriptional activation of NOXA by VSV or SV is independent of p53, but requires the presence of interferon regulatory factor 1 (IRF-1), IRF-3 and cAMP-responsive element binding protein (CREB). Binding to and transactivation of the NOXA promoter by each of these transcription factors is governed by post-translational modification involving different pathways for each factor. Thus, SV infection activates IRF-3 and CREB by phosphorylation triggered by Toll like receptor 3 signalling, and a pathway involving calcium-independent phopholipase A2, respectively. In addition transactivation induced by IRF-1 during viral infection correlates with a 10 kDa increase in its molecular weight, suggesting a covalent linkage with a previously unknown regulatory polypeptide.