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Evaluation of the effect of pyrimethamine, an anti-malarial drug, on HIV-1 replication

  1. Author:
    Oguariri, R. M.
    Adelsberger, J. W.
    Baseler, M. W.
    Imamichi, T.

  2. Author Address

    [Oguariri, Raphael M.; Imamichi, Tomozumi] NCI, Lab Human Retrovirol, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. [Adelsberger, Joseph W.; Baseler, Michael W.] NCI, AIDS Monitoring Lab, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. [Oguariri, Raphael M.; Adelsberger, Joseph W.; Baseler, Michael W.; Imamichi, Tomozumi] NCI, Clin Serv Program, Appl & Dev Directorate, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.;Oguariri, RM, NCI, Lab Human Retrovirol, Sci Applicat Int Corp Frederick Inc, Bldg 550,Room 204, Frederick, MD 21702 USA.;oguaririr@mail.nih.gov
    1. Year: 2010
    2. Date: Nov
  2. Journal: Virus Research
    1. 153
    2. 2
    3. Pages: 269-276
  4. Type of Article: Article
  5. ISSN: 0168-1702
  1. Abstract:

    Co-infection of human immunodeficiency virus (HIV) with malaria is one of the pandemic problems in Africa and parts of Asia. Here we investigated the impact of pyrimethamine (PYR) and two other clinical anti-malarial drugs (chloroquine [CO] or artemisinin [ART]) on HIV-1 replication. Peripheral blood mononuclear cells (PBMCs) or MT-2 cells were infected with HIVNL4.3 strain and treated with different concentrations of the anti-malarial drugs. HIV-1 replication was measured using p24 ELISA. We show that 10 mu M CQ and ART inhibited HIV-1 replication by 76% and 60% in PBMCs, respectively, but not in MT-2 cells. In contrast, 10 mu M PYR enhanced HIV-1 replication in MT-2 cells by >10-fold. A series of molecular mechanism studies revealed that PYR increased intracellular HIV gag proteins without affecting the promoter or the reverse transcriptase activity. The effect of PYR was independent of HTLV-1 produced by MT-2 cells. Of interest, PYR treatment led to S-phase accumulation and increased AZT and d4T antiviral activity by similar to 4-fold. Taken together, we show that PYR significantly enhances HIV-1 replication by affecting the cellular machinery. Our results could be relevant for the management of malaria and HIV particularly in regions where HIV-1 and malaria epidemics overlap. (C) 2010 Elsevier B.V. All rights reserved.

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External Sources

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  2. DOI: 10.1016/j.virusres.2010.08.018
  3. View record in Web of Science®
  4. WOS: 000283605100012

Library Notes

  1. Fiscal Year: FY2010-2011
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