A Novel HIV-1 Latency System for Drug Discovery

DESCRIPTION (provided by applicant): Highly active antiretroviral therapy (HAART) has had an important impact upon morbidity and mortality from AIDS. Although HAART results in a remarkable suppression of HIV-1 replication in infected patients, it does not provide for elimination of the virus even after years of suppressive therapy. Contributing to the lack of viral clearance is the presence of latently infected cells in patients, which upon withdrawal of HAART, contribute to viral rebound. Attempts at eradicating latently infected cells by activating them with cytokines and lymphokines has not met with success probably owing both to the inability of this treatment to reach all of the latent viral reservoirs and to the toxicity of the regimen. Small molecules with pharmacological properties that allow them to reach all viral reservoirs and activate latent HIV-1 pro viruses could very well result in clearance of HIV-1 infections when used in combination with HAART, as HAART should control infections by the newly activated HIV-1 pro viruses while allowing elimination of the freshly activated cells because some viral proteins are cytotoxic and viral expression will induce an immune response against these cells. Here a latency vector reporter system will be developed to identify new drugs that can abrogate viral latency. T and monocyte cell lines harboring latent HIV-1 vector virus will be developed. Activation of latent virus will result in the expression of a marker gene that can be utilized for high throughput screening. This system should provide a safe, efficient and rapid system to discover novel drugs for eliminating HIV-1 infection.