Antiviral Activities in Human Saliva

Malamud, Daniel; Abrams, William R.; Barber, Cheryl; Weissman, Drew; Rehtanz, Manuela; Golub, Ellis E.

doi:10.1177/0022034511399282

Cited by 96 publications

(113 citation statements)

References 34 publications

Supporting

Mentioning

111

Contrasting

Order By: Relevance

“…Many different components of human saliva have been shown to have antibacterial and antiviral properties (24)(25)(26); one that is particularly active against influenza virus is the scavenger receptor-rich glycoprotein gp340, originally referred to as salivary agglutinin (4,7,27). This molecule, which acts as a ␥-inhibitor presenting sialic acid to block the receptorbinding site of HA, may have evolved to perform a function in humans similar to that of the mouse salivary inhibitor, but its potency in halting the progression of infection down the respiratory tree in humans or animal models remains unknown.…”

Section: Figmentioning

confidence: 99%

Salivary Blockade Protects the Lower Respiratory Tract of Mice from Lethal Influenza Virus Infection

Ivinson

Deliyannis

McNabb

et al. 2017

J Virol

View full text Add to dashboard Cite

It is possible to model the progression of influenza virus from the upper respiratory tract to the lower respiratory tract in the mouse using viral inoculum delivered in a restricted manner to the nose. In this model, infection with the A/Udorn/ 307/72 (Udorn) strain of virus results ultimately in high viral titers in both the trachea and lungs. In contrast, the A/Puerto Rico/8/34 (PR8) strain causes an infection that is almost entirely limited to the nasal passages. The factors that govern the progression of virus down the respiratory tract are not well understood. Here, we show that, while PR8 virus grows to high titers in the nose, an inhibitor present in the saliva blocks further progression of infection to the trachea and lungs and renders an otherwise lethal dose of virus completely asymptomatic. In vitro, the salivary inhibitor was capable of potent neutralization of PR8 virus and an additional 20 strains of type A virus and two type B strains that were tested. The exceptions were Udorn virus and the closely related H3N2 strains A/Port Chalmers/1/73 and A/Victoria/3/75. Characterization of the salivary inhibitor showed it to be independent of sialic acid and other carbohydrates for its function. This and other biochemical properties, together with its virus strain specificity and in vivo function, indicate that the mouse salivary inhibitor is a previously undescribed innate inhibitory molecule that may have evolved to provide pulmonary protection of the species from fatal influenza virus infection. IMPORTANCE Influenza A virus occasionally jumps from aquatic birds, its natural host, into mammals to cause outbreaks of varying severity, including pandemics in humans. Despite the laboratory mouse being used as a model to study influenza virus pathogenesis, natural outbreaks of influenza have not been reported in the species. Here, we shed light on one mechanism that might allow mice to be protected from influenza in the wild. We show that virus deposited in the mouse upper respiratory tract will not progress to the lower respiratory tract due to the presence of a potent inhibitor of the virus in saliva. Containing inhibitor-sensitive virus to the upper respiratory tract renders an otherwise lethal infection subclinical. This knowledge sheds light on how natural inhibitors may have evolved to improve survival in this species.KEYWORDS influenza, innate inhibitors I nfluenza A virus (IAV) is a respiratory pathogen of global significance, responsible for 250,000 to 500,000 deaths annually. Innate immunity is critical to the host in the early stages of IAV infection, restricting the escalation of viral loads prior to the induction of virus-clearing responses mediated by the adaptive immune system. As part of the innate immune system, a variety of soluble molecules are present in respiratory secretions to provide an initial barrier to infection. They include collectins, pentraxins,

show abstract

Section: Figmentioning

confidence: 99%

Salivary Blockade Protects the Lower Respiratory Tract of Mice from Lethal Influenza Virus Infection

Ivinson

Deliyannis

McNabb

et al. 2017

J Virol

View full text Add to dashboard Cite

show abstract

“…Consequently, besides supplying its components involved in the process of food digestion, saliva also plays an important role in maintaining the body's immunity by providing multiple immunogenic components (Malamud et al, 2011). In addition, saliva can also be used as a diagnostic medium for non-invasive examination of the animal condition (Kaufman and Lamster, 2002;Lamy and Mau, 2012).…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of a 14.2 kDa Protein Isolated from Bali Cattle(Bos Sondaicus/Javanicus)Saliva Using Single Dimension Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis and Matrix-Assisted Laser Desorption Ionization Time-of-Flight Tandem Mass Spectrometer

Depamede

2013

Italian Journal of Animal Science

View full text Add to dashboard Cite

A 14.2 kDa protein isolated from Bali cattle (Bos sondaicus/javanicus) saliva has been reported to have a bactericidal activity. The aim of this study was to analyse the nature of a 14.2 kDa protein using single dimension (1-D) sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometer (MALDI TOF/TOF). The protein was isolated by means of polyethylene glycol (PEG)/sodium sulfate aqueous twophase system, and then determined by 12.5% SDS-PAGE. A band of 14.2 kDa was sliced and analysed by MALDI TOF/TOF mass spectrometer using a 5800 proteomics analyzer. Mascot search and National Center for Biotechnology Information (NCBI) Blast search revealed that the spot of 1-D SDS-PAGE consisted of three proteins: zymogen granule protein 16 homologue B, pancreatic adenocarcinoma upregulated factor-like, and prolactin-inducible protein homologue precursor. The three proteins have been observed in Bos taurus and other species such as mouse. The actual nature of the proteins and their function in Bali cattle (Bos sondaicus/javanicus), as well as the connection with the evolution of bovines need further analysis.

show abstract

“…Therefore, gp340 is thought to be an important factor for mediating the host immune response against microbial infection. gp340 is known to bind many pathogens, including Gram-positive and -negative bacteria and viruses (4,11,12,13). This binding is mediated by a specific interaction between bacteria and gp340.…”

mentioning

confidence: 99%

Staphylococcus aureus SasA Is Responsible for Binding to the Salivary Agglutinin gp340, Derived from Human Saliva

et al. 2013

View full text Add to dashboard Cite

Staphylococcus aureus is a major human pathogen that can colonize the nasal cavity, skin, intestine, and oral cavity as a commensal bacterium. gp340, also known as DMBT1 (deleted in malignant brain tumors 1), is associated with epithelial differentiation and innate immunity. In the oral cavity, gp340 induces salivary aggregation with several oral bacteria and promotes bacterial adhesion to tissues such as the teeth and mucosa. S. aureus is often isolated from the oral cavity, but the mechanism underlying its persistence in the oral cavity remains unclear. In this study, we investigated the interaction between S. aureus and gp340 and found that S. aureus interacts with saliva-and gp340-coated resin. We then identified the S. aureus factor(s) responsible for binding to gp340. The cell surface protein SasA, which is rich in basic amino acids (BR domain) at the N terminus, was responsible for binding to gp340. Inactivation of the sasA gene resulted in a significant decrease in S. aureus binding to gp340-coated resin. Also, recombinant SasA protein (rSasA) showed binding affinity to gp340, which was inhibited by the addition of N-acetylneuraminic acid. Surface plasmon resonance analysis showed that rSasA significantly bound to the NeuAc␣(2-3)Gal␤(1-4)GlcNAc structure. These results indicate that SasA is responsible for binding to gp340 via the N-acetylneuraminic acid moiety.

show abstract

Antiviral Activities in Human Saliva

Cited by 96 publications

References 34 publications

Salivary Blockade Protects the Lower Respiratory Tract of Mice from Lethal Influenza Virus Infection

Salivary Blockade Protects the Lower Respiratory Tract of Mice from Lethal Influenza Virus Infection

Proteomic Analysis of a 14.2 kDa Protein Isolated from Bali Cattle(Bos Sondaicus/Javanicus)Saliva Using Single Dimension Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis and Matrix-Assisted Laser Desorption Ionization Time-of-Flight Tandem Mass Spectrometer

Staphylococcus aureus SasA Is Responsible for Binding to the Salivary Agglutinin gp340, Derived from Human Saliva

Contact Info

Product

Resources

About