Previous research has recognized that saliva contains factors which inhibit HIV-1 production or infectivity. The salivary HIV-inhibitory factors (SHIF) can be derived from salivary glands and immune systems such as lymphocytes and macrophages. Four hypotheses will be tested in the proposal: 1) There are unidentified SHIFs in addition to the reported factor such as secretory leukocyte protease-inhibitor (SLPI); 2) certain SHIFs (HIV bp) bind to viral envelop proteins and inhibit viral entry; 3) chemokines constitute one of SHIF; and 4) certain SHIFs compete with HIV-1 for receptors on T cells, or monocytes. To test the hypotheses, five specific aims are proposed. 1. To isolate and characterized SHIF cDNA from a subtractive expression cDNA libraries of parotid and submandibular/sublingual salivary glands. 2. To isolate and characterize cDNAs whose protein products (HIV bp) bind to HIV-1 gp120, from parotid and submandibular salivary gland cDNA libraries by yeast-based two-hybrid system. 3. To determine whether normal or AIDS patient's saliva contain macrophage or T cell-derived chemokines which display HIV-1-suppressive activities. 4. To determine whether the binding of HIV bp to gp120 inhibits HIV-1 attachment or subsequent stages of HIV-1 life cycle. 5. To determine whether certain SHIF such as chemokines and SLPI compete with HIV-1 for the binding to CD4+ T cells or monocytes, or inhibit other stage of HIV-1 life cycle. Identification of natural HIV-inhibitory defectors and determination of their action mechanisms are necessary for effective treatment of AIDS. Since individual isolates of HIV-1 shows difference in sensitivity to a certain inhibitory factors, identification of more inhibitory factors will aid in developing treatment modalities of AIDS.
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