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. 2009 Feb;24(1):18-24.
doi: 10.1111/j.1399-302X.2008.00468.x.

Multiple components contribute to ability of saliva to inhibit influenza viruses

M R White  1 , E J Helmerhorst, A Ligtenberg, M Karpel, T Tecle, W L Siqueira, F G Oppenheim, K L Hartshorn
Affiliations

Multiple components contribute to ability of saliva to inhibit influenza viruses

M R White (V体育ios版) et al. Oral Microbiol Immunol. 2009 Feb.

Abstract

Introduction: Saliva is a potentially important barrier against respiratory viral infection but its mechanism of action is not well studied. VSports手机版.

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. V体育安卓版.

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 V体育ios版. 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 VSports最新版本. Of interest, antiviral activity of saliva against IAV and HIV differs in terms of specific glandular secretions and proteins that are inhibitory. .

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V体育ios版 - Conflict of interest statement

The authors have no conflict of interest related to research presented in this manuscript.

"V体育官网" Figures

Fig. 1
Fig. 1
Saliva of healthy volunteers inhibits infectivity of influenza A virus (IAV). Whole saliva obtained from a panel of healthy volunteer donors was tested for the ability to neutralize the Phil82 strain of IAV using the infectious focus assay (A). Each saliva preparation caused significant dose-related reduction in viral infectivity. Results are expressed as mean % of control infectivity (n = 3 or more for each saliva sample). The neutralizing activity of whole saliva (supernatant or native), or parotid or SMSL secretions from three donors was compared (B). Neutralizing activity was present in all of these preparations (all P < 0.05 compared to control). Results were normalized to 200 μg/ml saliva protein.
Fig. 2
Fig. 2
Hemagglutination (HA) inhibitory activity of whole saliva or parotid or submandibular/sublingual (SMSL) secretions. Mean HA inhibitory activity of whole saliva (supernatant or native) was compared to that of parotid or SMSL secretions from three donors. SMSL secretions had significantly greater HA inhibitory activity than either whole saliva preparation (*P < 0.02) when for the amount of protein per saliva sample. Greater activity in this assay is reflected by a lower concentration of the saliva preparation needed to inhibit a fixed concentration (40 HAU) of IAV.
Fig. 3
Fig. 3
Histatins 1 and 3, MUC5B, and human neutrophil defensins (HNPs) inhibit the infectivity of influenza A virus (IAV). Inhibition of infectivity of the Phil82 strain of IAV was tested using the fluorescent focus assay as in Fig. 1. In the left panel more abundant salivary proteins [histatins, proline-rich proteins (PRPs), amylase, and MUC5B] were preincubated with the virus and then inoculated on Madin–Darby canine kidney cells. Histatins 1 and 3 and MUC5B significantly inhibited infectivity at all the concentrations tested (P < 0.01 compared to control for all). Results are mean ± SEM of three or more experiments. PRP, amylase, and histatin 5 did not inhibit infectivity. In the right panel less abundant salivary proteins were tested. Among these only HNPs 1 and 2 inhibited infectivity.
Fig. 4
Fig. 4
Salivary glycoprotein 340 (gp-340) inhibits neuraminidase (NA) activity of the PR-8 strain of influenza A virus (IAV). The PR-8 strain of IAV was preincubated with the indicated concentrations of salivary gp-340 isolated from two different saliva donors. Salivary gp-340 from donor #1 caused significantly more inhibition at concentrations of 0.4 and 0.8 μg/ml compared to that of donor #2 (results mean ± SEM of four experiments).
Fig. 5
Fig. 5
Oseltamivir and surfactant protein D (SP-D) have cooperative viral aggregating activity when combined with MUC5B. Viral aggregation was assessed by decreases in light transmission through a stirred suspension of Phil82 influenza A virus. The left panel shows the effect of adding oseltamivir (1 μg/ml) to MUC5B and the right panel the effect of adding SP-D (0.2 μg/ml) to MUC5B in this assay. MUC5B alone (8 μg/ml) caused a significant decrease in light transmission after 50 and 100 s but it was no longer different from control after that (n = 5; P < 0.05 compared to control at 50 and 100 s). Oseltamivir alone did not cause any aggregation but markedly potentiated the effect of MUC5B (significant at all time-points by analysis of variance). SP-D caused aggregation on its own and also increased activity of MUC5B. The combination of MUC5B and SP-D was significantly greater than MUC5B alone but not than SP-D alone by analysis of variance.
Fig. 6
Fig. 6
Oseltamivir and surfactant protein D (SP-D) potentiate viral neutralization and hemagglutination (HA) inhibition caused by MUC5B. In the left panel viral neutralization was measured as in Fig. 3. The Phil82 strain of virus was preincubated with the indicated concentrations of MUC5B alone or with MUC5B combined with either 250 ng/ml oseltamivir or 6 ng/ml human SP-D dodecamers. Inhibition caused by the combinations of either SP-D or oseltamivir with MUC5B caused significantly greater neutralization than either treatment alone (n = 5; significance assessed by analysis of variance). HA titers were measured on viral samples used in the aggregation assays shown in Fig. 5 and are shown in the right panel. The combination of oseltamivir and mucin caused markedly greater inhibition than either agent alone (n = 4; significant by analysis of variance as indicated by **). The combination of SP-D and MUC5B caused significantly greater inhibition than MUC5B alone but not than SP-D alone (indicated by *).
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