Research from Howard University, Center for Sickle Cell Disease in the area of HIV/AIDS genetics described
2007 NOV 12 -- Scientists discuss in 'Iron chelators ICL670 and 311 inhibit HIV-1 transcription' new findings in HIV/AIDS. "HIV-1 replication is induced by an excess of iron and iron chelation by desferrioxamine (DFO) inhibits viral replication by reducing proliferation of infected cells. Treatment of cells with DFO and 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) inhibit expression of proteins that regulate cell-cycle progression, including cycle-dependent kinase 2 (CDK2)," investigators in the United States report. "Our recent studies showed that CDK2 participates in HIV-1 transcription and viral replication suggesting that inhibition of CDK2 by iron chelators might also affect HIV-1 transcription. Here we evaluated the effect of a clinically approved orally effective iron chelator, 4-[3,5-bis-(hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid (ICL670) and 311 on HIV-1 transcription. Both ICL670 and 311 inhibited Tat-induced HIV-1 transcription in CEM-T cells, 293T and HeLa cells. Neither ICL670 nor 311 induced cytotoxicity at concentrations that inhibited HIV-1 transcription. The chelators decreased cellular activity of CDK2 and reduced HIV-1 Tat phosphorylation by CDK2," wrote Z. Debebe and colleagues, Howard University, Center for Sickle Cell Disease. The researchers concluded: "Neither ICL670A or 311 decreased CDK9 protein level but significantly reduced association of CDK9 with cyclin T1 and reduced phosphorylation of Ser-2 residues of RNA polymerase II C-terminal domainour findings add to the evidence that iron chelators can inhibit HIV-1 transcription by deregulating CDK2 and CDK9. Further consideration should be given to the development of iron chelators for future anti-retroviral therapeutics." Debebe and colleagues published their study in Virology (Iron chelators ICL670 and 311 inhibit HIV-1 transcription. Virology, 2007;367(2):324-33). For additional information, contact Z. Debebe, Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC 20060 USA.. The publisher of the journal Virology can be contacted at: Academic Press Inc. Elsevier Science, 525 B St., Ste. 1900, San Diego, CA 92101-4495, USA. Keywords: United States, Washington, HIV/AIDS Genetics, AIDS, Acquired Immunodeficiency Syndrome, HIV, Hematology, Human Immunodeficiency Virus, Sickle Cell Anemia, Sickle Cell Disease, Virology. This article was prepared by AIDS Weekly editors from staff and other reports. Copyright 2007, AIDS Weekly via NewsRx.com.
|
