The Division of AIDS of the National Institute of Allergy and Infectious Diseases supports research to promote progress in the treatment and prevention of HIV disease. Traditionally, emphasis has been placed on the in vitro testing of antivirals in conventional cell culture-based assay systems of acute or chronic HIV infection with an accepted, though limited, number of standard virological end points. However, as the scientific basis upon which the understanding of the process of HIV infection is founded has evolved and matured, innovative strategies have become viable options to consider. The capability to integrate cutting edge laboratory findings into the development and performance of relevant, specific assays of efficacy distinguishes the capabilities of this contract. The primary activity of the contract is the evaluation of therapies/strategies, alone and in combination, in specialized (cell-based and target-based) assays. Such therapies/strategies include: (a) CD4-dependent and CD4-independent assays to evaluate inhibitors of the transmission of HIV from infected to uninfected cells; (b) an assay to monitor the effect of mucin on the effectiveness of transmission inhibitors identified above; (c) an assay to monitor the toxicity of transmission inhibitors to H2O2-secreting Lactobacillus (i.e., beneficial vaginal flora); and (d) biochemical and cell based assays to identify inhibitors of HIV regulatory proteins (e.g., Tat, Rev, etc.) and associated host cell factors. The contract also possesses the capability to: (a) design and develop expression systems (bacterial, insect, yeast, or mammalian) to optimize expression of selected proteins from HIV, related lentiviruses and/or host cells; (b) produce and purify the desired target proteins in amounts sufficient for use in relevant assays; (c) develop, evaluate, and/or validate standardized protocols for specialized assays; (d) produce standardized reagents (e.g., virus stocks and cell lines).
