Suppression of HIV-1 infection by a small molecule inhibitor of the ATM kinase
- PMID: 15834407
- DOI: 10.1038/ncb1250
Suppression of HIV-1 infection by a small molecule inhibitor of the ATM kinase
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.
Comment in
-
ATM: HIV-1's Achilles heel?Nat Cell Biol. 2005 May;7(5):452-3. doi: 10.1038/ncb0505-452. Nat Cell Biol. 2005. PMID: 15867928 No abstract available.
Similar articles
-
ATM: HIV-1's Achilles heel?Nat Cell Biol. 2005 May;7(5):452-3. doi: 10.1038/ncb0505-452. Nat Cell Biol. 2005. PMID: 15867928 No abstract available.
-
Extracellular signal-related kinase positively regulates ataxia telangiectasia mutated, homologous recombination repair, and the DNA damage response.Cancer Res. 2007 Feb 1;67(3):1046-53. doi: 10.1158/0008-5472.CAN-06-2371. Cancer Res. 2007. PMID: 17283137
-
Inhibition of HIV-1 replication by caffeine and caffeine-related methylxanthines.Virology. 2005 May 10;335(2):177-84. doi: 10.1016/j.virol.2005.02.015. Virology. 2005. PMID: 15840517
-
DNA repair in HIV-1 infection: a case for inhibitors of cellular co-factors?Curr HIV Res. 2006 Oct;4(4):411-21. doi: 10.2174/157016206778560027. Curr HIV Res. 2006. PMID: 17073616 Review.
-
HIV type 1 integrase inhibitors: from basic research to clinical implications.AIDS Rev. 2008 Jul-Sep;10(3):172-89. AIDS Rev. 2008. PMID: 18820719 Review.
Cited by
-
Deregulation of DNA damage signal transduction by herpesvirus latency-associated M2.J Virol. 2006 Jun;80(12):5862-74. doi: 10.1128/JVI.02732-05. J Virol. 2006. PMID: 16731925 Free PMC article.
-
A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling.Cell. 2006 May 19;125(4):733-47. doi: 10.1016/j.cell.2006.03.035. Epub 2006 Apr 27. Cell. 2006. PMID: 16647110 Free PMC article.
-
Induction of a pro-apoptotic ATM-NF-kappaB pathway and its repression by ATR in response to replication stress.EMBO J. 2008 Jul 23;27(14):1963-73. doi: 10.1038/emboj.2008.127. Epub 2008 Jun 26. EMBO J. 2008. PMID: 18583959 Free PMC article.
-
The role of unintegrated DNA in HIV infection.Retrovirology. 2011 Jul 1;8:52. doi: 10.1186/1742-4690-8-52. Retrovirology. 2011. PMID: 21722380 Free PMC article. Review.
-
Ataxia telangiectasia-mutated-Rad3-related DNA damage checkpoint signaling pathway triggered by hepatitis B virus infection.World J Gastroenterol. 2008 Oct 28;14(40):6163-70. doi: 10.3748/wjg.14.6163. World J Gastroenterol. 2008. PMID: 18985806 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous
