One of the factors present in saliva which has been shown to inhibit HIV infection in vitro is secretory leukocyte protease inhibitor (SLPI). This application is a proposal for an R01 award to extend the work of the PI on the inhibition of HIV by SLPI. The overall objective is to determine the molecular mechanism through which SLPI blocks virus infectivity. Since all of the studies to date have utilized laboratory strains of HIV, the first specific aim is designed to determine if SLPI also inhibits primary clinical isolates of HIV-1 which are thought to be more representative of the strains found in infected individuals. Isolates that are found to be resistant to SLPI will be further characterized by generating recombinant chimeras in order to identify the region(s) of virus responsible for the resistant phenotype.
In specific aim 2, the investigator will generate SLPI-based recombinant proteins using alanine scanning, deletion and site-directed mutagenesis. The mutants will be used to test the hypothesis that charged amino acid residues on the exterior of the SLPI molecule are responsible for inhibition of HIV.
