Personal Info:

RESEARCH

During HIV replication, the integration of the HIV genome into the cellular chromosome is an essential step, which is catalyzed by the viral enzyme integrase. Recent findings suggest that cellular co-factors are also involved in the integration process in vivo.
In this project we want to expand the knowledge on the relevant function of the putative co-factors in the integration process. We want to identify new cellular co-factors. Our approach is based on a proprietary integrase over-expression system in mammalian cells, based on a synthetic integrase gene. We created stable cell lines that express various forms of HIV-1 integrase. Growth kinetics of the cell lines is indistinguishable from the parental cells, implying compensatory changes in the cells. These changes may point to proteins and/or pathways interacting with integrase and integration. Therefore, we will measure the alterations in mRNA and protein content of cells expressing wild type or enzymatically inactive integrase to assess the impact of this DNA modifying enzyme on the cellular metabolism. This will ultimately lead to a better insight into the HIV-1 integration process and could provide new possible targets for antiviral drug or gene therapy, to be included in the current antiretroviral combination therapies for HIV-infected patients.

First Name: Wim Position: Post-Doc
Last Name: Pluymers Address: Molecular Virology and Gene Therapy
E-mail: Wim.pluymers@med.kuleuven.ac.be   Minderbroederstraat 10
Tel: (0032) 16 33 21 82   3000 Leuven, Belgium
Fax: (0032) 16 33 21 31 Date of Birth: 09/03/1973

Papers:

  • Vandergeyten S., Mol K., Pluymers W., Kühn E.R. and Darras V. (1998)

    Changes in plasma T-3 during fasting/refeeding in tilapia (Oreochromis niloticus) are mainly regulated through changes in hepatic type II iodothyronine deiodinase Fish. Physiology and Biochemistry 19(2): 135-143

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  • Pluymers W., Cherepanov P., Schols D., De Clercq E., and Debyser Z. (1999)

    Nuclear localization of human immunodeficiency virus type 1 integrase expressed as a fusion protein with green fluorescent protein. Virology 258:327-332.

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  • Cherepanov P., Surratt D., Toelen J., Pluymers W., Griffith J., De Clercq E., and Debyser Z. (1999)

    Activity of recombinant HIV-1 integrase on mini-HIV DNA. Nucleic Acids Res 27:2202?2210.

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  • Witvrouw M, Fikkert V., Pluymers W., Mathews B., Mardel K., Schols D., Raff J., Debyser Z, De Clercq E., Holan G. and Pannecouque C. (2000)

    Polyanionic (i.e. Polysulfonate) dendrimers can inhibit the replication of human immunodeficiency virus (HIV) by interfering with both virus adsorption and later steps (reverse transcriptase/integrase) in the virus replicative cycle. Molecular Pharmacology 58(5): 1100-1108

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  • Pluymers W., Pannecouque C., Fikkert V., Neamati N., Marchand C., Burke T.R. Jr., Pommier Y., De Clercq E., Debyser Z. and Witvrouw M. (2000)

    Viral entry as the primary target of anti-HIV activity of chicoric acid and its tetra-acetyl esters. Molecular Pharmacology 58: 641-648.

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  • Pluymers W., Cherepanov P., Claeys A., Proost P., De Clercq E., and Debyser Z. (2000)

    High-level expression of active HIV-1 integrase from a synthetic gene in human cells. FASEB J. 14:1389?1399.

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  • Debyser Z., Cherepanov P., Pluymers W., and De Clercq, E. (2001)

    Assays for the evaluation of HIV-1 integrase inhibitors. Methods in Molecular Biology. Nucleases. (Humana Press, Ed. C. H. Schein) 160, 139-155

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  • Pluymers W., DeClercq E. and Debyser Z. (2001)

    HIV-1 integrase as a target for antiretroviral therapy: a review. Curr. Drug Targets Infect. Disord. 1(2): 133-149

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  • Pluymers W., Pannecouque C., Van Maele B., Tetz V., Cherepanov P., De Clercq E., Witvrouw M. and Debyser Z. (2002)

    New class of HIV integrase inhibitors that block viral replication in cell culture Curr Biol 12: 1169-1177.

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  • Pluymers W., Pais G., Van Maele, B., Pannecouque C., Fikkert V., Burke T. R. Jr., De Clercq E., Witvrouw M., Neamati N. and Debyser Z. (2002)

    Inhibition of human immunodeficiency virus type 1 integration by diketo derivatives. Antimicrob Agents Chemother 46: 3292-3297.

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  • Maertens G, Cherepanov P, Pluymers W, Busschots K, De Clercq E, Debyser Z, Engelborghs Y. (2003)

    LEDGF/p75 Is Essential for Nuclear and Chromosomal Targeting of HIV-1 Integrase in Human Cells. J Biol Chem. 278(35):33528-33539.

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