Secretory leukocyte protease inhibitor: a human saliva protein exhibiting anti-human immunodeficiency virus 1 activity in vitro.

Abstract

Infection of adherent primary monocytes with HIV-lBa.L is significantly suppressed in the presence of human saliva. By reverse transcriptase (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 infectivity. Antiviral activity was identified in the saliva soluble fraction, and to determine the factor (s) responsible, individual saliva proteins were examined. Of those proteins examined, only secretory leukocyte protease inhibitor (SLPI) was found to possess anti-HIV-1 activity at physiological concentrations. SLPI anti-HIV-1 activity was dose dependent, with maximal inhibition at 1-10 gg/ml (> 90% inhibition of RT activity). SLPI also partially inhibited HIV-111B infection in proliferating human T cells. SLPI appears to target a host cell-associated molecule, since no interaction with viral proteins could be demonstrated. However, SLPI anti-HIV-1 activity was not due to direct interaction with or downregulation of the CD4 antigen. Partial depletion of SLPI in whole saliva resulted in decreased anti-HIV-1 activity of saliva. These data indicate that SLPI has antiretroviral activity and may contribute to the important antiviral activity of saliva associated with the infrequent oral transmission of HIV-1. (J. Clin. Invest. 1995. 96:456-464.)

Tonsil Epithelial Factors May Influence Oropharyngeal Human Immunodeficiency Virus Transmission

“…50 The mechanism through which SLPI exerts its anti-viral action was previously shown to involve a host cell molecule and not to target the virus itself and to occur early in the viral life cycle. 5,6 Finally, the architectural uniqueness of the crypt epithelium probably also contributes to HIV transmission vulnerability in the tonsil. In the area of the crypt, the epithelium is thinner and has multiple breaks that may provide portals of entry for the virus while creating a less accessible environment to the anti-viral components of saliva, including SLPI.…”

“…The oral cavity is considered a relatively protected mucosal site where the innate host defense molecules of saliva are capable of neutralizing HIV and the epithelium itself is not receptive for transmission. [3][4][5][6][7][8] Orogenital transmission has a very low per-contact risk of acquiring infection, with estimates that 4 of 10,000 contacts result in infection compared with heterosexual or homosexual genital contact (1 of 200 to 1000). 9 -12 Vertical transmission from mother to infant during breast feeding also occurs with varying rates but may be as high as 15% when breast-feeding is prolonged.…”

Murine Macrophages Produce Secretory Leukocyte Protease Inhibitor During Clearance of Apoptotic Cells: Implications for Resolution of the Inflammatory Response

“…Further investigation revealed that macrophages and neutrophils are rich sources of SLPI, and SLPI has been recognized to have antibacterial, antiviral, and antiinflammatory properties. These include the prevention of HIV replication in monocytic cells (12,13), the down-regulation of prostaglandin, and matrix metalloprotease synthesis by monocytes (14), and the inhibition of inflammatory lung injury caused by deposition of IgG-immune complexes (15), or of joint damage caused by bacterial cell wall-induced arthritis (16). We have previously found that serum SLPI is elevated in human sepsis and experimental endotoxemia (17), and that SLPI expression in murine macrophages is induced by LPS and lipotechoic acid (18,19) but suppressed by IFN-␥ (18).…”

The Effect of Liposome Encapsulation on the Pharmacokinetics of Recombinant Secretory Leukocyte Protease Inhibitor (rSLPI) Therapy after Local Delivery to a Guinea Pig Asthma Model

“…Its abundance in the upper respiratory tract suggests that the primary role of SLPI is to provide an anti-Neutrophil Elastase (anti-NE) shield for the tracheobronchial tree (Fryksmark et al, 1982, Mooren et al, 1983. SLPI has also been found to possess anti-bacterial, anti-viral and antiinflammatory activity including the ability to reduce nuclear factor-B (NF-B) activation intracellularly (Greene et al, 2004, Jin et al, 1997, Lentsch et al, 1999, McNeely et al, 1995, Taggart et al, 2002, Zhang et al, 1997. rSLPI is therefore a highly promising therapeutic for inflammatory lung disease.…”