The comparative inhibitory potency of salivary mucins against human immunodeficiency virus type 1.

MUC5B and MUC7 salivary mucins are reported to inhibit HIV-1 entry into target cells in vitro; however, their relative inhibitory potencies have not been quantitively compared. There is also conflicting evidence regarding whether HIV-1 infection diminishes mucins' inhibitory efficacy. We explored the effect of donor HIV-1 status upon the anti-HIV-1 potency of purified MUC5B and MUC7 while comparing their relative inhibitory potential using a pseudovirus-based neutralization assay. HIV status of sample donors had no detectable effect on HIV-1 inhibition by salivary mucins. MUC5B (median IC50 50 µg/ml, IQR 10-116 µg/ml) exhibited significantly more potent HIV-1 inhibition than MUC7 (median IC50 458 µg/ml, IQR 192->2000 µg/ml; Mann-Whitney U p < 0.0001). We suggest that larger size, gel-forming properties and extensive glycosylation of MUC5B allow more effective binding and aggregation of viral particles. MUC5B is also more abundant in the saliva and is therefore likely to make a substantially greater contribution to it's anti-HIV-1 properties.

Mechanisms of astringency: Structural alteration of the oral mucosal pellicle by dietary tannins and protective effect of bPRPs.

The interaction of tannins with salivary proteins is involved in astringency. This paper focussed on saliva lining oral mucosae, the mucosal pellicle. Using a cell-based model, the impact of two dietary tannins (EgC and EgCG) on the mucosal pellicle structure and properties was investigated by microscopic techniques. The role of basic Proline-Rich-Proteins (bPRPs) in protecting the mucosal pellicle was also evaluated. At low (0.05 mM) tannin concentration, below the sensory detection threshold, the distribution of salivary mucins MUC5B on cells remained unaffected. At 0.5 and 1 mM, MUC5B-tannin aggregates were observed and their size increased with tannin concentration and with galloylation. In addition, 3 mM EgCG resulted in higher friction forces measured by AFM. In presence of bPRPs, the size distribution of aggregates was greatly modified and tended to resemble that of the "no tannin" condition, highlighting that bPRPs have a protective effect against the structural alteration induced by dietary tannins.

Histatins enhance wound closure with oral and non-oral cells.

The role of human saliva in oral wound-healing has never been fully elucidated. We previously demonstrated that parotid-salivary histatins enhance in vitro wound closure. The question remains whether other salivary-gland secretions enhance wound closure, and also the effects of histatins on primary and non-oral cells. Since the presence of histatins is not limited to parotid saliva, we expected to observe wound-closure activity of other salivary-gland secretions. However, here we show that non-parotid saliva does not stimulate wound closure, most probably due to the presence of mucins, since the addition of MUC5B to parotid saliva abolished its effect. Furthermore, we found that histatins stimulated wound closure of (primary) cells of both oral and non-oral origin. This suggests that the cellular receptor of histatins is widely expressed and not confined to cells derived from the oral cavity. These findings encourage the future therapeutic application of histatins in the treatment of all kinds of wounds.

Multiple components contribute to ability of saliva to inhibit influenza viruses.

INTRODUCTION: Saliva is a potentially important barrier against respiratory viral infection but its mechanism of action is not well studied. METHODS: We tested the antiviral activities of whole saliva, specific salivary gland secretions, and purified salivary proteins against strains of influenza A virus (IAV) in vitro. RESULTS: Whole saliva or parotid or submandibular/sublingual secretions from healthy donors inhibited IAV based on hemagglutination inhibition and neutralization assays. This differs from human immunodeficiency virus (HIV), for which only submandibular/sublingual secretions are reported to be inhibitory. Among purified salivary proteins, MUC5B, scavenger receptor cysteine-rich glycoprotein 340 (salivary gp-340), histatins, and human neutrophil defensins (HNPs) inhibited IAV at the concentrations present in whole saliva. In contrast, some abundant salivary proteins (acidic proline-rich proteins and amylase) had no activity, nor did several other less abundant salivary proteins with known activity against HIV (e.g. thrombospondin or serum leukocyte protease inhibitor). Whole saliva and MUC5B did not inhibit neuraminidase activity of IAV and viral neutralizing and aggregating activity of MUC5B was potentiated by the neuraminidase inhibitor oseltamivir. Hence, MUC5B inhibits IAV by presenting a sialic acid ligand for the viral hemagglutinin. The mechanism of action of histatins requires further study. CONCLUSIONS: These findings indicate that saliva represents an important initial barrier to IAV infection and underline the complexity of host defense activity of oral secretions. Of interest, antiviral activity of saliva against IAV and HIV differs in terms of specific glandular secretions and proteins that are inhibitory.