Strategy may overcome antiretroviral drug resistance
A theoretical strategy for blocking HIV growth and tackling drug resistance is published in Nature Cell Biology this month.
Alan Lau, of KuDOS Pharmaceuticals, and colleagues show that HIV-1 integrase
activates a protein called ATM produced by the ataxia-telangiectasia-mutated
gene. This protein is a key mediator in the cellular response to DNA
damage.
The researchers found that ATM is essential to the survival of infected
HIV-1 cells since it helps to repair DNA damage caused by viral integration
into the host cell genome.
They demonstrate that a recently identified specific small molecule inhibitor
of ATM kinase — KU-55933 — leads to increased cell death
and has the potential to suppress replication of both wild-type and drug-resistant
HIV-1. ATM is not essential for the survival of non-infected cells.
Most treatments for HIV target virally
encoded proteins that are rapidly mutating, which often leads to the
development of drug resistance during therapy. This strategy addresses
the problem by targeting non-essential host cell proteins that are required
for viral replication (2005;7:493). |
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