HIV Inhibitor in Saliva Identified Through CRADA
- The following article apeared in the Antiviral Agents Bulletin, May 1995, p. 136.
- HIV Inhibitor in Saliva Identified
- Drs. T. McNeely and S. Wahl, National Inst. of Dental Research (NIDR, NIH; Bethesda, MD), in collaboration with Dr. S.P. Eisenberg, Synergen, Inc. (Boulder, CO; now part of Amgen Corp.), recently reported identifying a protein, secretory leukocyte protease inhibitor (SLPI), in human saliva that inhibits HIV-1. This may explain why HIV-infection is not spread by saliva (except in some rare instances). Although HIV can be readily recovered from the saliva of infected persons, the concentration is low and recovery is infrequent. Various studies have shown that saliva prevents in vitro HIV-infection of lymphocytes and monocytes. This research was carried out through a Collaborative Research and Development Agreement (CRADA) between Synergen and NIDR, which means that Synergen has the option to exclusively license this invention. Synergen and NIH have jointly filed patent applications including WO 9406454.
- SLPI (pronounced 'slippy'; formerly called factor A) is a small protein that has been shown to attach to the surface of blood cells and block infection by HIV. The researchers report, ÒSLPI is found in varying levels in the coating of most mucous membranes, and is believed to be a natural protector against the bodyÕs own protein-destroying enzymes... Saliva present for 1 hour during exposure of monocytes to virus [HIV-1Ba-L] inhibited HIV propagation for three weeks post-infection.Ó SLPI was isolated from saliva and found to have potent anti-HIV activity at physiological levels. HIV inhibition was dose-dependent and over 90% inhibition of HIV reverse transcriptase activity was observed at 1-10 µg/ml. SLPI also inhibited HIVIIIB infection in proliferating peripheral blood mononuclear cells. SLPI appears to target a host cell-associated molecule, since anti-HIV activity was observed when SLPI was preincubated with human monocytes. No interaction with viral proteins was detectable and SLPI activity was not due to interaction with or down-regulation of CD4+ receptors. The researchers are now attempting to identify the SLPI receptor and SLPIÕs mechanism of action of HIV inhibition. The extent of SLPI activity in fluids other than saliva has not been determined.