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• W2068563189 abstract "Objectives: Herpes simplex virus (HSV) infections have been associated with reactivation of HIV-1 replication and increases of HIV-1-load in plasma of co-infected individuals. The present authors have previously reported that in epithelial cells HSV-1 induces the IκB-kinase (IKK) causing persistent activation of NF-κB, a critical regulator of HIV-1 replication. The present study was performed to investigate whether HSV-1-infection could induce IKK-mediated NF-κB activation and enhance HIV-1 expression in human T cells, and to analyze the effect of the IKK-inhibitor prostaglandin A1 (PGA1) and other prostanoids on the NF-κB-mediated HSV-HIV interaction. Design and methods: Induction of IKK and NF-κB activity was determined in lymphoblastoid Jurkat cells and HIV-1 chronically-infected H9 and ACH-2 cells by kinase assay and electrophoretic mobility shift assay, respectively. The effect of HSV-1 and different prostanoids on HIV-1 expression and replication was determined in Jurkat cells transfected with HIV-1-LTR-driven reporter genes, and in H9 and ACH-2 cells by p24-antigen level evaluation. The role of NF-κB in HSV-1-induced HIV-1 expression was investigated by using the IκBα dominant-negative IκBα-AA in co-transfection experiments. Results: In human T lymphoblastoid cells HSV-1 potently induces IKK activity, causing a persistent induction of NF-κB. HSV-1-induced IKK and NF-κB function results in transactivation of HIV-1-LTR-regulated genes and induction of HIV-1 replication in chronically-infected T cells. The cyclopentenone PGA1 inhibits HSV-1-induced IKK and NF-κB activities, blocking HIV-1-LTR-driven expression and preventing HSV-1-induced HIV-1 replication in co-infected cells. Conclusions: The results indicate that IKK is a key factor in triggering HSV-1-induced HIV-1 transcription in chronically-infected cells and identify cyclopentenone prostanoids as potent inhibitors of HSV-1-induced HIV-1 reactivation." @default.
• W2068563189 created "2016-06-24" @default.
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• W2068563189 date "2004-06-01" @default.
• W2068563189 modified "2023-10-12" @default.
• W2068563189 title "Inhibition of herpesvirus-induced HIV-1 replication by cyclopentenone prostaglandins" @default.
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• W2068563189 doi "https://doi.org/10.1097/00002030-200406180-00005" @default.
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