Salivary Defense Factors in Herpes Simplex Virus Infection

Abstract

Saliva may contribute to a lowering of the infectious herpes simplex virus (HSV) dose during transmission and consequently abrogate infection or lead to decreased reactivation. To test this hypothesis, we assayed saliva for innate defense factors, immunoglobulin content, and the capacity to interfere with HSV infection. Serum or salivary anti-HSV IgG levels did not correlate with control of recurrent labial herpes (RLH) and were significantly higher in subjects with RLH compared with asymptomatic seropositive subjects. Although no differences in levels or output rate of innate defense factors between the groups were observed, the salivary neutralizing activity correlated with lactoferrin and hypothiocyanite concentrations in the asymptomatic seropositive group. Our results suggest that saliva contains factors, in addition to anti-HSV immunoglobulins, that neutralize HSV and may indirectly contribute to the control of RLH.

Get full access to this article

View all access options for this article.

References

Bergey EJ, Gu M, Collins AR, Bradway SD, Levine MJ -1993-. Modulation of herpes simplex virus type 1 replication by human salivary secretions. Oral Microbiol Immunol 8:89–93.

Björck L, Grubb A, Kjellén L -1990-. Cystatin C, a human proteinase inhibitor, blocks replication of herpes simplex virus. J Virol 64:941–943.

Bolscher JGM, Groenink J, van der Kwaak JS, van den Keijbus PAM, van ‘t Hof W, Veerman ECI, et al. -1999-. Detection and quantification of MUC7 in submandibular, sublingual, palatine, and labial saliva by anti-peptide antiserum. J Dent Res 78:1362–1369.

Brice SL, Leahy MA, Ong L, Krejci S, Stockert SS, Huff JC, et al. -1994-. Examination of non-involved skin, previously involved skin, and peripheral blood for herpes simplex virus DNA in patients with recurrent herpes-associated erythema multiforme. J Cutan Pathol 21:408–412.

Cisani G, Varaldo PE, Pompei R, Valisena S, Satta G -1989-. Cell fusion induced by herpes simplex is inhibited by hen egg-white lysozyme. Microbios 59:73–83.

Crouse CA, Pflugfelder SC, Pereira I, Cleary T, Rabinowitz S, Atherton SS -1990-. Detection of herpes viral genomes in normal and diseased corneal epithelium. Curr Eye Res 9:569–581.

Douglas RG Jr, Couch RB -1970-. A prospective study of chronic herpes simplex virus infection and recurrent herpes labialis in humans. J Immunol 104:289–295.

Gu M, Haraszthy GG, Collins AR, Bergey EJ -1995-. Identification of salivary proteins inhibiting herpes simplex virus 1 replication. Oral Microbiol Immunol 10:54–59.

Gyselink R, Coles D, Ash RJ, Fritz ME -1978-. Salivary neutralizing activity against herpes simplex virus type 1. J Infect Dis 137:583–586.

10.

Hasegawa K, Motsuchi W, Tanaka S, Dosako S -1994-. Inhibition with lactoferrin of in vitro infection with human herpes virus. Jpn J Med Sci Biol 47:73–85.

11.

Heineman HS, Greenberg MS -1980-. Cell-protective effect of human saliva specific for herpes simplex virus. Arch Oral Biol 25:257–261.

12.

Henskens YM, van den Keijbus PA, Veerman EC, Van der Weijden GA, Timmerman MF, Snoek CM, et al. -1996-. Protein composition of whole and parotid saliva in healthy and periodontitis subjects. Determination of cystatins, albumin, amylase, and IgA. J Periodontal Res 31:57–65.

13.

Kameyama T, Sujaku C, Yamamoto S, Hwang CBC, Shillitoe EJ -1988-. Shedding of herpes simplex virus type 1 into saliva. J Oral Pathol 17:478–481.

14.

Kaufman HE, Brown DC, Ellison EM -1967-. Recurrent herpes in the rabbit and man. Science 156:1628–1629.

15.

Kirstilä V, Tenovuo J, Ruuskanen O, Suonpää J, Meurman O, Vilja P -1996-. Longitudinal analysis of human salivary immunoglobulins, nonimmune antimicrobial agents, and microflora after tonsillectomy. Clin Immunol Immunopathol 80:110–115.

16.

Koskinen P, Vuorinen T, Meurman O -1987-. Influenza A and B virus IgG and IgM serology by enzyme immunoassays. Epidem Inf 99:55–64.

17.

Lenander-Lumikari M, Loimaranta V -2000-. Saliva and dental caries. Adv Dent Res 14:40–47.

18.

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ -1951-. Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275.

19.

Martin ML, Palmer EL, Kissling RE -1972-. Complement-fixing antigens of herpes simplex virus types 1 and 2: reactivity of capsid, envelope and soluble antigens. Infect Immun 5:248–254.

20.

Mikola H, Waris M, Tenovuo J -1995-. Inhibition of herpes simplex virus type 1, respiratory syncytial virus and echovirus type 11 by peroxidase-generated hypothiocyanite. Antiviral Res 26:161–171.

21.

Pourtois M, Binet C, Van Tieghem N, Courtois P, Vandenabbeele A, Thiry L -1990-. Inhibition of HIV infectivity by lactoperoxidase-produced hypothiocyanite. J Biol Buccale 18:251–253.

22.

Spruance SL -1984-. Pathogenesis of herpes simplex labialis: excretion of virus in the oral cavity. J Clin Microbiol 19:675–679.

23.

Tateishi K, Toh Y, Minagawa H, Tashiro H -1994-. Detection of herpes simplex virus -HSV- in the saliva from 1,000 oral surgery outpatients by the polymerase chain reaction -PCR- and virus isolation. J Oral Pathol Med 23:80–84.

24.

Wheeler CE -1988-. The herpes simplex problem. J Am Acad Dermatol 18:163–168.

25.

Zakay-Rones Z, Ehrlich J, Hochman N, Levy R -1973-. The sulcular epithelium as a reservoir for herpes simplex virus in man. J Periodontol 44:779–781.

26.

Ziegler T, Waris M, Rautiainen M, Arstila P -1988-. Herpes simplex virus detection by macroscopic reading after overnight incubation and immunoperoxidase staining. J Clin Microbiol 26:2013–2017.