Like many other mucosal surfaces, the oral cavity is exposed to a variety of infectious agents and toxic compounds. To provide a variety of biological functions (communication, nutrient intake, respiratory activity, etc), it needs to be an open system, yet this requires an equally diverse group of activities/biomolecules to insure its continued viability. Thus, copious salivary flow is important for mastication, taste, the maintenance of hard tissue structure, and the prevention of a range of toxic and infectious assaults. In this article, we focus on one aspect of the role of saliva—namely, protection from infection, specifically via the innate immune system. This system is an important first-line defense against bacterial and viral infection. In addition, mucosal surfaces are typically coated by a protective layer of mucins. Although salivary flow plays a major role in the continuous cleansing of the oral cavity (Dawes, 2008), we focus here on proteins in the oral cavity that demonstrate both antibacterial and antiviral activity.
To obtain an overview of antimicrobial proteins present in saliva, we carried out a PubMed search of the literature (http://www.ncbi.nlm.nih.gov/pubmed/
). The lists the major proteins found in saliva and documented to demonstrate antibacterial activity. Though not exhaustive, this list contains proteins shown to be either bacteriostatic or bacteriocidal against multiple bacterial species. Of interest, most of these proteins have been reported to be antiviral for at least one virus. As noted on the table, the only entities reported having antibacterial but not antiviral activity are the histatins and calprotectin.
Salivary Antibacterial and Antiviral Activities
Despite the range of antiviral activities found in saliva, many reports still identify viruses in saliva, often infectious—including HSV, HIV, VZV, EBV, HPV, hepatitis A, hepatitis C, Ebola, Norwalk virus, HHV 6 and 8, measles, rabies, adenoviruses, and prions. Although infectious virus in the presence of potent antiviral activity appears counterintuitive, there are potential explanations (as suggested in the Discussion section).
Our studies have focused on a salivary protein initially identified as possessing antibacterial activity but subsequently found to have potent inhibitory activity against HIV-1. Significantly, this activity is manifest against only HIV-1 and influenza A (Wu et al., 2003
; White et al., 2005a
), with little or no activity against HSV, adenovirus, HIV-2, or SIV. This protein was referred to as salivary agglutinin
and is now more commonly called gp340 or DMBT-1 (Wu et al., 2004
). outlines the timeline of these discoveries. From 1986 to 1988, a series of publications—first by Fultz (1986)
and then Fox et al. (1988
)—reported that incubation of HIV-1 in human or chimpanzee saliva resulted in a loss of infectivity. Many groups subsequently began to report a variety of salivary proteins demonstrating anti-HIV activity (Archibald and Cole, 1990
; Bergey et al., 1993a
; Malamud et al., 1993
; McNeely et al., 1995
). In 1997, we reported that the effect of saliva on HIV inhibition was directly on the virus and specific for HIV-1 (Malamud et al., 1997
), and in 1998 we demonstrated that salivary agglutinin could inhibit HIV infectivity by binding to gp120 on the surface of the virus (Nagashunmugam et al., 1998
). Subsequent cloning of gp340 (Holmskov et al., 1999
) and proteomic analysis by Prakobphol et al. (2000)
identified salivary agglutinin as a previously cloned protein, DMBT-1 or gp340.
Timeline of salivary agglutinin (SAG; i.e., gp340) antibacterial and anti-HIV-1 activity.