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• W1569011485 endingPage "8180" @default.
• W1569011485 startingPage "8174" @default.
• W1569011485 abstract "ABSTRACT Protein tyrosine kinase (PTK) phosphorylation is involved in cellular proliferation and differentiation processes that are key factors for human immunodeficiency virus type 1 (HIV-1) regulation in infected monocytic cells. Short-term exposure of the chronically infected promyelocytic OM10 cell line with the PTK inhibitor genistein induced a dose-dependent increase in p24 antigen production in culture supernatants. This induction persisted in the presence of the reverse transcriptase inhibitor, zidovudine, and was associated with an increased transcription of HIV-1 multiply spliced and unspliced RNAs, suggesting a transcriptional mechanism targeting the integrated provirus. Genistein induced cell differentiation, apoptosis, and a G 2 arrest in the OM10 cells. Cell differentiation and apoptosis were not directly involved in the observed increase in HIV-1 replication that was closely linked to genistein-induced G 2 arrest. Alleviation of the G 2 arrest by pentoxyfylline resulted in a concomitant reduction of HIV-1 to baseline replication. Additionally, by flow cytometry, a significant increase in the number of p24 antigen-expressing cells was observed in cells arrested in G 2 compared to those located in G 1 or S. Tyrosine kinase inhibition was found not to be essential for enhanced viral replication, which seemed to be related to two other properties of genistein, inhibition of topoisomerase II activity and inhibition of phosphotidylinositol turnover. These findings are consistent with the recent observation that HIV-1 Vpr induces viral replication through preventing proliferation of cells by arresting them in G 2 of the cell cycle and strongly suggest that manipulation of the cell cycle plays an important role in HIV-1 pathogenesis." @default.
• W1569011485 created "2016-06-24" @default.
• W1569011485 creator A5017306542 @default.
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• W1569011485 date "1998-10-01" @default.
• W1569011485 modified "2023-10-11" @default.
• W1569011485 title "Human Immunodeficiency Virus Type 1 Induction Mediated by Genistein Is Linked to Cell Cycle Arrest in G ₂" @default.
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• W1569011485 doi "https://doi.org/10.1128/jvi.72.10.8174-8180.1998" @default.
• W1569011485 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/110162" @default.
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