Identification of salivary proteins inhibiting herpes simplex virus 1 replication

Abstract

Salivary proteins play an important role in the maintenance of the oral ecology. Previous studies have indicated that human submandibular-sublingual and parotid salivas can selectively suppress the in vitro infectivity of herpes simplex virus 1. The purpose of this study was to identify the salivary components in human submandibular-sublingual saliva that modulate in vitro infectivity. Assessment of the interaction of viral particles with salivary components was accomplished using an in vitro solid-phase assay. These experiments revealed that herpes simplex virus particles selectively interact with the members of the salivary proline-rich protein and cystatin families. Subsequent yield reduction assays demonstrated the ability of proline-rich proteins and salivary cystatins to inhibit the viral replication, with basic proline-rich peptides being more effective. Subsequent assays suggest that basic proline-rich peptides reduced the virus titer by interfering with penetration and/or cellular processing of virus within the target cell. Collectively, these results further suggest that salivary proteins have an important role in the host defense mechanism against recurrent herpesvirus infection.

Does Variability in Salivary Protein Concentrations Influence Oral Microbial Ecology and Oral Health?

“…These proteins may play a minor role in regulating salivary calcium (Shomers et al, 1982;Al-Hashimi and Levine, 1989;Lamkin and Oppenheim, 1993), but may act mainly as cysteine-proteinase inhibitors . Cystatins may inhibit bacterial proteases involved in the pathogenesis of periodontal disease, and they may also interfere with in vitro infection by herpes simplex virus (Gu et al, 1995). Another isoform, cystatin C, is present in both saliva and serum .…”

“…This reveals a cryptic epitope (cryptitope) which may promote the adherence of many oral bacteria, including streptococci (Gibbons et al, 1991), actinomyces species (Gibbons et al, 1988), and Porphyromonas gingivalis (Amano et al, 1994). bPRP functions are less well-known, but a recent study suggests that they may inhibit the infectivity of herpes simplex virus (Gu et al, 1995). Statherin is a small phosphoprotein which may play a primary role in maintaining calcium equilibrium (Hay et al, 1984).…”

Interaction of Plant Polyphenols with Salivary Proteins

“…Less desirable is the ability of APRPs to mediate binding of bacteria to hydroxyapatite, since it may assist in the formation of dental plaque (Gibbons et al ., 1988;Kataoka et al ., 1997). BPRPs have anti-viral activity (Gu et al ., 1995) and bind to C. albicans (O'Sullivan et al ., 1997), which may affect the colonization of oral surfaces by these micro-organisms.…”

The cysteine protease inhibitors cystatins inhibit herpes simplex virus type 1-induced apoptosis and virus yield in HEp-2 cells

“…Björck et al (1990) showed that human recombinant cystatin C inhibited HSV-1 replication in green monkey kidney cells. In addition, proline-rich proteins and salivary cystatins were able to inhibit HSV-1 replication (Gu et al, 1995). In contrast, the level of cystatins in saliva did not correlate with HSV-neutralizing activity (Välimaa et al, 2002).…”

“…In addition to their other biological functions, cystatins have been shown to inhibit RNA virus-induced programmed cell death (Björklund et al, 1997). Moreover, the antiviral properties of cystatins (Björck et al, 1990;Aoki et al, 1995;Gu et al, 1995;Collins & Grubb, 1998) suggest that they may also inhibit cysteine proteases used by viruses during infection.…”