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- Title
Analysis of the Signal Transduction Pathway Leading to Human Immunodeficiency Virus-1-Induced Interferon Regulatory Factor-1 Upregulation.
- Authors
SGARBANTI, MARCO; MARSILI, GIULIA; REMOLI, ANNA LISA; RIDOLFI, BARBARA; STELLACCI, EMILIA; BORSETTI, ALESSANDRA; ENSOLI, BARBARA; BATTISTINI, ANGELA
- Abstract
Interferon (IFN) regulatory factors (IRFs) constitute a family of transcriptional activators and repressors involved in the regulation of immune system, host defense, and cell growth. All members share conserved DNAbinding domains that recognize DNA sequences termed IRF-binding elements/ IFN-stimulated response elements (IRF-E/ISRE) present on the promoter of IFN-α/β and IFN-stimulated genes. An ISRE has been identified downstream of the transcription start site of the long terminal repeat (LTR) of human immunodeficiency virus-1 (HIV-1). Our previous results showed that among the IRF factors, IRF-1 is able to stimulate HIV-1 LTR transcription and its expression is induced by HIV-1, early, upon infection and before the expression of Tat. In this study we investigated the signal transduction pathway leading to HIV- 1-induced IRF-1 expression. Key IRF-1 promoter elements that mediate the activation of transcription upon induction by inflammatory cytokines are IFN-γ-activated sequences that bind members of the signal transducer and activator of transcription (STAT) family and binding sites for nuclear factor κB (NF-κB). Both STAT-1 and NF-κB activation were examined to determine putative molecular targets whose inhibition resulted in the inhibition of HIV-1 replication. The results show that at early time points after HIV-1 infection, NF-κB but not STAT-1 is activated. Moreover, a significant decrease in HIV-1 replication was observed upon de novo infection of Jurkat T cells expressing an NF-κB superrepressor (IκB-α2NΔ 4). These results suggest that in early phases of HIV-1 infection, before detectable cytokine production, NF-κB seems responsible for HIV-1-induced IRF-1 expression.
- Subjects
CELLULAR signal transduction; HIV infections; INTERFERONS; CYTOKINES; TRANSCRIPTION factors
- Publication
Annals of the New York Academy of Sciences, 2004, Vol 1030, Issue 1, p187
- ISSN
0077-8923
- Publication type
Article
- DOI
10.1196/annals.1329.024