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Stimulation of human immunodeficiency virus type 1 expression by ceramide
B Papp1, D Zhang, J E Groopman
1Division of Hematology/Oncology, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02215.
Insights
Ceramide significantly boosts human immunodeficiency virus type 1 (HIV-1) production in myeloid cells by enhancing viral transcription. This suggests the tumor necrosis factor-ceramide pathway regulates HIV-1 expression.
Area of Science:
- Cell Biology
- Virology
- Immunology
Background:
- Ceramide is an intracellular lipid mediator of tumor necrosis factor alpha (TNF-alpha) action.
- Human immunodeficiency virus type 1 (HIV-1) establishes latency in myelomonocytic cells.
- Understanding HIV-1 latency regulation is crucial for therapeutic strategies.
Purpose of the Study:
- To investigate the effect of ceramide on HIV-1 gene expression in latently infected myeloid cell lines.
- To determine the mechanism by which ceramide influences HIV-1 production.
Main Methods:
- Treatment of latently infected U-1IIIB and OM-10.1 myelomonocytic cells with ceramide.
- Measurement of HIV production enhancement.
- Transfection of U-937 cells with a reporter gene construct (chloramphenicol acetyltransferase) under the control of the HIV-1 long terminal repeat (LTR).
Main Results:
- Ceramide treatment led to a 20- to 100-fold enhancement of HIV production in U-1IIIB and OM-10.1 cells.
- Ceramide enhanced the expression of the HIV-1 LTR-directed reporter gene in transfected U-937 cells.
- These findings indicate ceramide acts at the transcriptional level to upregulate HIV-1 expression.
Conclusions:
- The tumor necrosis factor-ceramide signaling pathway may play a role in regulating HIV-1 expression.
- Ceramide enhances HIV-1 production by increasing viral transcription.
- Targeting the TNF-ceramide system could be a potential strategy for managing HIV-1 in myeloid cells.
Abstract:
Ceramide, an intracellular lipid mediator of tumor necrosis factor alpha (TNF-alpha) action, was studied for its effects on the expression of the proviral human immunodeficiency virus type 1 genome in latently infected myelomonocytic cell lines U-1IIIB and OM-10.1. Ceramide treatment resulted in a 20- to 100-fold enhancement of HIV production in these cells. Ceramide also enhanced the expression of the chloramphenicol acetyltransferase gene directed by a human immunodeficiency virus type 1 long terminal repeat in transfected U-937 cells, indicating that ceramide acts at the level of viral transcription. These observations suggest that the TNF-ceramide signaling system may be involved in the regulation of HIV expression in certain myeloid cell types.