With the recognition that acquired immunodeficiency syndrome (AIDS) is a major worldwide health concern and that the causative agent, human immunodeficiency virus type I (HIV-I) threatens to infect tens of thousands of Americans yearly, the elucidation of effective preventive and therapeutic strategies for combating this invariably fatal disease is of prime importance in the scientific community. Although blood, semen and genital secretions can be viewed as the major hazardous bodily fluids, others such as milk and saliva cannot be overlooked. Saliva can be passed from an infected subject to an uninfected subject via sexual or non-sexual activities. It is also a secretion that possesses both non-immunoglobulin inhibitory activity towards HIV-I and, in the infected subject, specific immunoglobulins to HIV-I. The extent to which the saliva of infected individuals represents a biohazard to others, and the saliva of uninfected individuals protects them from infection, is unknown. The long term objectives of this study are to elucidate the nature, mechanism of action and relative effectiveness of both the non-immunoglobulin salivary inhibitors and the salivary immunoglobulins directed against HIV-I in healthy and in infected patients at various stages of their disease.
The specific aims are: (1) to identify, isolate and characterize those non- immunoglobulin components of parotid and extra-parotid saliva that inhibit HIV-I infectivity; (2) to elucidate the mechanism of action whereby the non-immunoglobulin salivary inhibitor(s) interfere with HIV-I infection of host cells; (3) to determine the salivary inhibition of HIV-I infectivity of non-infected and infected subjects at various stages of their disease, and to assess the relative contributions of the non-immunoglobulin factors and immunoglobulins to the total anti-HIV-I activity of the saliva in infected subjects. Parotid and extra-parotid salivas will be obtained from uninfected subjects and subjected to a battery of chromatographic procedures in order to isolate those components that inhibit HIV infectivity. Once such component(s) is/are isolated, they will be characterized structurally and with respect to mechanism of action by means of chemical analyses, competitive inhibition experiments and specific immunological and other inhibition techniques. Parotid saliva from subjects at various stages of HIV-I infection will be analyzed for specific antibody isotypes directed toward HIV-I. The relative and absolute degree of HIV-inhibition by non-immunoglobulin factors in the salivas of non-infected and infected subjects will be assessed. In this way, the true protectiveness of the inhibitors in non-infected subjects and, conversely, the true hazard potential of saliva from infected subjects can be assessed. This information will help health care authorities evaluate the appropriateness of barrier and other protective methodology in the care delivery system and in personal hygiene. The knowledge of the nature and mechanism of action of the non-immunoglobulin inhibitors of HIV-I infectivity may also open avenues for the development of more effective preventive and/or therapeutic agents for AIDS.
| Robinovitch, M R; Ashley, R L; Iversen, J M et al. (2001) Parotid salivary basic proline-rich proteins inhibit HIV-I infectivity. Oral Dis 7:86-93 |
