SECRETORY LEUKOCYTE PROTEASE INHIBITOR - A HUMAN SALIVA PROTEIN EXHIBITING ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS-1 ACTIVITY IN-VITRO

Infection of adherent primary monocytes with HIV-1(Ba-L) is significan tly suppressed in the presence of human saliva, By reverse transcripta se (RT) levels, saliva, although present for only 1 h during monocyte viral exposure, inhibited HIV-1 infectivity for 3 wk after infection, whereas human plasma and synovial fluid failed to inhibit HIV-1 infect ivity, Antiviral activity was identified in the saliva soluble fractio n, and to determine the factor(s) responsible, individual saliva prote ins were examined, Of those proteins examined, only secretory leukocyt e protease inhibitor (SLPI) was found to possess anti-HTV-1 activity a t physiological concentrations, SLPI anti-HIV-l activity was dose depe ndent, with maximal inhibition at 1-10 mu g/ml (> 90% inhibition of RT activity), SLPI also partially inhibited HIV-1(IIIB) infection in pro liferating human T cells, SLPI appears to target a host cell-associate d molecule, since no interaction with viral proteins could be demonstr ated. However, SLPI anti-HIV-1 activity was not due to direct interact ion with or downregulation of the CD4 antigen, Partial depletion of SL PI in whole saliva resulted in decreased anti-HIV-1 activity of saliva , These data indicate that SLPI has antiretroviral activity and may co ntribute to the important antiviral activity of saliva associated with the infrequent oral transmission of HIV-1.