Studies have demonstrated HIV-1 inhibitory activity in human saliva, which is predominately associated in the secretions obtained from the submandibular/sublingual glands (HSMSL). Electron microscopic techniques have demonstrated aggregation of HIV-1 particles by HSMSL, but not HPS. Further experiments suggested that a soluble form of HIV envelope glycoprotein 120 (rgp 120) interacts with the low molecular weight salivary glycoprotein, MG2. Mucins are the major organic components of the mucous layer that coats the epithelial cell surface, protecting them from environmental and microbial insult. These surfaces include the epithelia of the digestive, reproductive and respiratory tracts of all mammals. Although the peptide and carbohydrate structures of the various mucins found on these surfaces show differences, there rheological properties are very similar. In sexual transmission, HIV must traverse this coating to infect the underlying cells. However the role of mucins in modulating HIV pathogenicity of the epithelial surface has yet to be established. It is therefore the long term goal of this project o examine the role of the sialomucins in modulation of human immunodeficiency virus infectivity. To achieve this goal, we propose to use the salivary mucins as an assessable human model to better understand of how these macromolecules function in the modulation of HIV-1 pathogenesis. Our hypothesis is that mucins selectively interact with HIV particles thereby modulating the pathogenicity of the virus.
In Specific Aim 1, we will further assess the mechanism of inhibition of HIV by salivary mucin, MG2. MG2 was chosen because of its availability in purified form and is one of the best characterized of all the known mucins.
For Specific Aims 2, we will evaluate the """"""""spectrum"""""""" of mucins in regard to inhibition of selected HIV strains. Finally, Specific Aim 3 will assess the functional inhibition of HIV infection by mucins in cell to cell transmission. Assessment of the ability of sialomucins to negate this potential transmission is crucial to the protection of the host. The results of these studies are being used to examine, in detail, mechanism(s) whereby sialomucins exerts its effect on HIV/target cell interactions. It is anticipated that these studies will provide further information regarding the anti-HIV properties mucins, as well some insight to the relationship between HIV and other mucosal surfaces. Such knowledge could be invaluable for clinicians (both dentists and physicians), the scientific community at large, and the general public.
