Werner's syndrome helicase as a target for anti -HIV/AIDS therapy

摘要

Werner's Syndrome helicase (WRN) interacts in Tat/TAR-RNA chromatin-remodeling complexes assembled on the HIV-1 LTR to promote transcriptional activation and viral replication. WRN markedly increases basal HIV-1 transcription and synergizes with Tat to support LTR trans-activation. Inhibition of WRN functions, through expression of the trans-dominant-negative WRN_K577M mutant, potently represses HIV-1 LTR trans-activation and prevents intracellular synthesis of p24^Gag and inhibits virus production in HIV-infected H9_HIV-1IIIB lymphocytes. Therefore, the present disclosure provides a novel target for anti-HIV therapy. Methods and compositions of the disclosure may be used to perform high throughput screens for small molecule anti-HIV therapeutics. Such therapeutics may inhibit a stage in the HIV replicative cycle not affected by current anti-HIV drugs.