6th International AIDS Conference


San Francisco, California, USA — June 20-23, 1990

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Mechanism of HIV-1 induction in T-lymphocytes and monocytes by sodium butyrate: the role of the TATA box.

Int Conf AIDS 1990 Jun 20-23; 6:323 (abstract no. 1038)
Golub EI, Li G, Volsky DJ; St. Luke's/Roosevelt Hospital Center and College of Physicians & Surgeons, Columbia Univ., New York, NY, USA

OBJECTIVE: To study the effect of sodium butyrate (NaB), a cell-differentiating agent, on HIV-1 replication in acutely and chronically infected cells, and on transcriptional activity of HIV-1 LTR.

METHODS: Effect of NaB on HIV-1 expression was tested during acute infection, in chronically infected monocytes (U1.1) and T-cells (ACH-2), or after transfection with HIV-1 DNA. HIV-1 replication was monitored by an assay for viral core antigen (p24 protein) and indirect immunofluorescence staining for HIV-1 antigens (IF). Effect of NaB on HIV-1 transcriptional control elements was tested in transient cat expression assays using plasmids which carry the cat gene under control of the HIV-1 LTR. Plasmids with mutations in different regulatory elements were used to identify LTR sequences involved in HIV-1 induction by NaB.

RESULTS: Addition of NaB (.1-5 mM) to chronically infected U1.1 or ACH-2 cells resulted in a rapid (3-24 h), dose-dependent induction of HIV-1 replication, and an increase in the proportion of HIV-1-expressing cells (from less than 0.5% to greater than 90%). NaB also facilitated primary infection of T-cells with HIV-1 and increased HIV-1 replication in cells transfected with HIV-1 DNA. Mutations which removed the negative regulatory region of HIV-1 LTR or which inactivated the HIV-1 enhancer had no effect on induction by NaB. In contrast, mutations which damage the TATA box completely abolished the inductive effects of NaB.

CONCLUSION: NaB is an extremely effective inducer of HIV-1 replication in T-cells and monocytes. The TATA box of HIV-1 is directly involved in this induction.

Keywords: AEGIS, HIV-1, Monocytes, HIV Long Terminal Repeat, TATA Box, T-Lymphocytes, Virus Replication, HIV Enhancer, Butyric Acid, HIV Core Protein p24, Transfection, HIV Antigens, Anti-HIV Agents, Cats, Animal, genetics, virology, ICA6KWDaegis,hiv-1,monocytes,hivlongterminalrepeat,tatabox,t-lymphocytes,virusreplication,hivenhancer,butyricacid,hivcoreproteinp24,transfection,hivantigens,anti-hivagents,cats,animal,genetics,virology,ica6

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