THE USE OF HIV-1 INTEGRASE IN SCREENING HIV-1 DRUG CANDIDATES

摘要

The present invention harnesses the roles of IN to screen drug candidates to inhibit HIV-1. The present invention uses IN mutants and fusion proteins to assess the effectiveness of a drug candidate in inhibiting a native IN function. The retrovirus integrase protein (IN) is essential for integration of the viral DNA into host cell chromosomes as well as for retroviruses in general. The ability of a drug candidate to inhibit retroviral replication utilizes a monitoring system such as a host cell culture infected with a retrovirus. After exposing the monitoring system to the drug candidate, the retroviral life cycle within the monitoring system is monitored and compared to monitoring system life cycle function of integrase mutant retrovirus. Alternatively, an integrase fusion protein of either vpr or vpx is added to a monitoring system infected with a retrovirus expressing wild-type integrase following exposure to a drug candidate. Changes in retrovirus life cycle function are monitored for suppression of a wild-type integrase function indicating retroviral replication has been comprised.