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A transcription inhibitor, Actinomycin D, enhances HIV-1 replication through an interleukin-6-dependent pathway

  1. Author:
    Imamichi, T.
    Conrads, T. P.
    Zhou, M.
    Liu, Y. X.
    Adelsberger, J. W.
    Veenstra, T. D.
    Lane, H. C.

  2. Author Address

    NIAID, Lab Human Retrovirol, Appl & Dev Res Program, SAIC Frederick, Frederick, MD 21702 USA. SAIC Frederick, Lab Proteom & Analyt Technol, Frederick, MD USA. SAIC Frederick, AIDS Monitoring Lab, Frederick, MD USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA Imamichi, T, NIAID, Lab Human Retrovirol, Appl & Dev Res Program, SAIC Frederick, Bldg 550,Room 126, Frederick, MD 21702 USA
    1. Year: 2005
    2. Date: DEC 1
  2. Journal: Jaids-Journal of Acquired Immune Deficiency Syndromes
    1. 40
    2. 4
    3. Pages: 388-397
  4. Type of Article: Article
  1. Abstract:

    We previously demonstrated that Actinomycin D (ActD) enhanced HIV-1 replication in the MT-2 cell, a human T-cell leukemia virus type-1-infected cell line. The MT-2 cell is known to produce multiple cytokines spontaneously. In this study, we investigated the impact of ActD on the cytokine production from MT-2 cells and HIV-1 replication in a latently infected cell line, U1. MT-2 cells were pulse-treated with 0 or 200 nM of ActD, and culture supernatants were collected 3 days after incubation. Supernatants from untreated cells (Sup0) induced HIV-1 replication by 150-fold in U1 cells. Culture supernatants from ActD-treated cells (Sup200) enhanced HIV-1 replication by 1200-fold. A combination of a sequential chromatographic approach and mass spectrometric analysis identified that the HIV-inducing factors in Sup200 were interleukin (IL)-6 and tumor necrosis factor (TNF)-beta. Quantitative analysis revealed that ActD treatment increased the concentration of IL-6 in Sup200 by 600% compared with that in Sup0 but decreased the amount of TNF beta in Sup200 by 85%. Northern blot analysis showed that ActD treatment increased IL-6 transcripts; however, no change was seen in TNF beta transcripts. These results suggest that ActD induces replication of HIV-1 through modulation of cytokine production

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External Sources

  1. View record in Web of Science®
  2. WOS: 000233474400002

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