Now, Lau and colleagues show that HIV type-1 (HIV-1) activates a cellular protein called ataxia-telangiectasia-mutated (ATM) a key mediator in the cellular response to DNA damage ndash; which is mutated in a rare genetic disease that can lead to cancer and premature ageing. The researchers find that ATM helps to repair DNA damage caused by viral integration in the host cell genome and is therefore essential to the survival of infected cells.
By Nature Cell Biology, [RxPG] A protein that can be specifically inhibited in order to block HIV growth is published in the May issue of Nature Cell Biology. Current drugs against HIV target viral proteins that are rapidly mutating, and so suffer from the inherent problem of drug-resistant variants arising during therapy. This new research could allow the development of a new therapy that is effective against all HIV strains, substantially reducing the likelihood of drug resistance.
At present, patients are treated with a cocktail of drugs that target several essential viral proteins to inhibit viral life cycles. These drugs are effective in reducing patient mortality, but the number of patients who are infected with multidrug-resistant variants is rapidly rising, creating a serious medical challenge.
Now, Lau and colleagues show that HIV type-1 (HIV-1) activates a cellular protein called ataxia-telangiectasia-mutated (ATM) a key mediator in the cellular response to DNA damage ndash; which is mutated in a rare genetic disease that can lead to cancer and premature ageing. The researchers find that ATM helps to repair DNA damage caused by viral integration in the host cell genome and is therefore essential to the survival of infected cells. Treating HIV-1-infected cells with the recently identified ATM-specific small molecule inhibitor KU-55933 leads to increased cell death and suppression of both wild-type and drug-resistant HIV-1 replication. However, ATM is not essential for organismal survival, making it an enticing therapeutic target in cancer therapy also.
If effective in animal and clinical studies, KU-55933 may provide a new class of anti-HIV inhibitors one that targets host cell proteins that are essential for retroviral growth. This provides new possibilities for overcoming the HIV drug resistance problem.
Publication:
Suppression of HIV-1 infection by a small molecule inhibitor of the ATM kinase; Alan Lau, Karra M. Swinbank, Parvin S. Ahmed, Debra L. Taylor, Stephen P. Jackson, Graeme C. M. Smith & Mark J. O'Connor; Published online: 17 April 2005 | doi:10.1038/ncb1250
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