Multiple components contribute to ability of saliva to inhibit influenza viruses.
BACKGROUND
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.
White
M R
MR
Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Helmerhorst
E J
EJ
Ligtenberg
A
A
Karpel
M
M
Tecle
T
T
Siqueira
W L
WL
Oppenheim
F G
FG
Hartshorn
K L
KL
D000998:Antiviral Agents / Q000494:pharmacology*; D023082:Defensins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D006385:Hemagglutination Inhibition Tests; D054808:Histatins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects*; D055257:Mucin-5B / Q000378:metabolism / Q000494:pharmacology; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009500:Neutralization Tests; D053139:Oseltamivir / Q000494:pharmacology; D010306:Parotid Gland / Q000378:metabolism; D011485:Protein Binding; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D012463:Saliva / Q000276:immunology*; D012471:Salivary Proteins and Peptides / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology*; D013363:Submandibular Gland / Q000378:metabolism
D000998:Antiviral Agents; D023082:Defensins; D004791:Enzyme Inhibitors; D054808:Histatins; C524578:MUC5B protein, human; D055257:Mucin-5B; D037663:Pulmonary Surfactant-Associated Protein D; D011971:Receptors, Immunologic; D012471:Salivary Proteins and Peptides; C116303:glycoprotein 340; D053139:Oseltamivir; D009439:Neuraminidase