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    Nat Cell Biol. 2005 May;7(5):493-500. Epub 2005 Apr 17.

    Suppression of HIV-1 infection by a small molecule inhibitor of the ATM kinase.

    Source

    KuDOS Pharmaceuticals Limited, 327 Cambridge Science Park, Milton Road, Cambridge CB4 0WG, UK.

    Abstract

    Chemotherapy that is used to treat human immunodeficiency virus type-1 (HIV-1) infection focuses primarily on targeting virally encoded proteins. However, the combination of a short retroviral life cycle and high mutation rate leads to the selection of drug-resistant HIV-1 variants. One way to address this problem is to inhibit non-essential host cell proteins that are required for viral replication. Here we show that the activity of HIV-1 integrase stimulates an ataxia-telangiectasia-mutated (ATM)-dependent DNA damage response, and that a deficiency of this ATM kinase sensitizes cells to retrovirus-induced cell death. Consistent with these observations, we demonstrate that a novel and specific small molecule inhibitor of ATM kinase activity, KU-55933, is capable of suppressing the replication of both wild-type and drug-resistant HIV-1.

    PMID:
    15834407
    [PubMed - indexed for MEDLINE]

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