Inhibition of HIV-1 IIIB and clinical isolates by human parotid, submandibular, sublingual and palatine saliva
Jan G. M. Bolscher
Department of Dental Basic Sciences, Section Oral Biochemistry, Academic Center for Dentistry Amsterdam,
Search for more papers by this authorKamran Nazmi
Department of Dental Basic Sciences, Section Oral Biochemistry, Academic Center for Dentistry Amsterdam,
Search for more papers by this authorLeonie J. Ran
Department of Clinical Viro-Immunology, CLB Sanquin and Laboratory for Experimental and, Clinical Immunology of the University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorFrank A. C. Van Engelenburg
Department of Clinical Viro-Immunology, CLB Sanquin and Laboratory for Experimental and, Clinical Immunology of the University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorHanneke Schuitemaker
Department of Clinical Viro-Immunology, CLB Sanquin and Laboratory for Experimental and, Clinical Immunology of the University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorEnno C. I. Veerman
Department of Dental Basic Sciences, Section Oral Biochemistry, Academic Center for Dentistry Amsterdam,
Search for more papers by this authorArie V. Nieuw Amerongen
Department of Dental Basic Sciences, Section Oral Biochemistry, Academic Center for Dentistry Amsterdam,
Search for more papers by this authorJan G. M. Bolscher
Department of Dental Basic Sciences, Section Oral Biochemistry, Academic Center for Dentistry Amsterdam,
Search for more papers by this authorKamran Nazmi
Department of Dental Basic Sciences, Section Oral Biochemistry, Academic Center for Dentistry Amsterdam,
Search for more papers by this authorLeonie J. Ran
Department of Clinical Viro-Immunology, CLB Sanquin and Laboratory for Experimental and, Clinical Immunology of the University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorFrank A. C. Van Engelenburg
Department of Clinical Viro-Immunology, CLB Sanquin and Laboratory for Experimental and, Clinical Immunology of the University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorHanneke Schuitemaker
Department of Clinical Viro-Immunology, CLB Sanquin and Laboratory for Experimental and, Clinical Immunology of the University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorEnno C. I. Veerman
Department of Dental Basic Sciences, Section Oral Biochemistry, Academic Center for Dentistry Amsterdam,
Search for more papers by this authorArie V. Nieuw Amerongen
Department of Dental Basic Sciences, Section Oral Biochemistry, Academic Center for Dentistry Amsterdam,
Search for more papers by this authorAbstract
Human saliva is known to possess components that decrease the HIV-1 infectivity in vitro. The mechanism of how these components inhibit the infectivity is still not clear on the molecular level. The purpose of this study was to discriminate between serous and mucous components with respect to inhibitory capacity and site of action. We have used total saliva and saliva from the major (sero)mucous glands: submandibular gland, sublingual glands, and glands in the palate, in comparison with the serous parotid glands. HIV-1 IIIB and primary variants were incubated with saliva, and inhibition of HIV-1-infection was determined by analysing the cytopathic effect on MT-2 cells. Mucous saliva, as well as serous saliva, contained high molecular weight components that reduced HIV-1-infectivity, at least partially by entrapment of the virus particles. Lower molecular weight components in all types of saliva possessed strong HIV-1 neutralizing capacity. Using pro-viral DNA synthesis by reverse transcription as a discrimination point in the replication cycle, the results indicated that part of the saliva samples acted before, but others after, this point. In conclusion, saliva inhibits HIV-1-infection by the action of high molecular weight components in combination with low molecular weight components from serous as well as mucous saliva, affecting different stages of the infection cycle.
References
- 1
Groopman JE,
Salahuddin SZ,
Sarngadharan MG,
Markham PD,
Gonda M,
Sliski A,
Gallo RC.
HTLV-III in saliva of people with AIDS-related complex and healthy homosexual men at risk for AIDS.
Science
1984; 226: 149–156.
10.1126/science.6093247 Google Scholar
- 2 Friedland GH, Saltzman BR, Rogers MF, Kahl PA, Lesser ML, Mayers MM, Klein RS. Lack of transmission of HTLV-III/LAV to household contacts of patients with AIDS or AIDS-related complex with oral candidasis. N Engl J Med 1986; 314: 344–349.
- 3 Barr CE, Miller LK, Lopez MR, Croxson TS, Schwartz SA, Denman H, Jandorek, R. Recovery of infectious HIV-1 from whole saliva. J Am Dent Assoc 1992; 123: 36–48.
- 4 Moore BE, Flaitz CM, Coppenhaver DH, Nichols C, Kalmaz GD, Bessman JD, Cloyd MW, Lynch DP, Prabhakar BS, Baron S. HIV recovery from saliva before and after dental treatment: inhibitors may have critical role in viral inactivation. J Am Dent Assoc 1993; 124: 67–74.
- 5 Goto Y, Yeh CK, Notkins AL, Prabhaker BS. Detection of proviral sequences in saliva of patients infected with human immunodeficiency virus type 1. AIDS Res Hum Retrovir 1991; 7: 343–347.
- 6 Yeung SC, Kazazi F, Randle CG, Howard RC, Rizvi N, Downie JC, Donovan BJ, Cooper DA, Sekine H, Dwyner DE, Cunningham AL. Patients infected with human immunodeficiency virus type 1 have low levels of virus in saliva even in the presence of periodontal disease. J Infec Dis 1993; 167: 803–809.
- 7 Fultz PN. Components of saliva inactivate human immunodeficiency virus. Lancet 1986; 2: 1215.
- 8 Fox PC, Wolff A, Yeh C-K, Atkinson JC, Baum BJ. Saliva inhibits HIV-1 infectivity. J Am Dent Assoc 1988; 116: 635–637.
- 9 Fox PC, Wolff A, Yeh C-K, Atkinson JC, Baum BJ. Salivary inhibition of HIV-infectivity: functional properties and distribution in men, women and children. J Am Dent Assoc 1989; 118: 709–711.
- 10 Archibald DW, Cole GA. In vitro inhibition of HIV-1 infectivity by human salivas. AIDS Res Hum Retrovir 1990; 6: 1425–1432.
- 11 Yeh C-K, Handelman B, Fox PC, Baum BJ. Further studies of salivary inhibition of HIV-1 infectivity. J AIDS 1992; 5: 898–903.
- 12 Malamud D, Friedman HM. HIV in the oral cavity: virus, viral inhibitory activity, and antiviral antibodies: a review. Crit Rev Oral Biol Medical 1993; 4: 461–466.
- 13 Malamud D, Davis C, Berthold P, Roth E, Friedman H. Human submandibular saliva aggregates HIV. AIDS Res Hum Retrovir 1993; 7: 633–637.
- 14 McNeeley TB, Dealy M, Dripps DJ, Orenstein JM, Eisenberg SP, Wahl SM. Secretory leukocyte protease inhibitor: a human salivary protein exhibiting anti-human immunodeficiency virus 1 activity in vitro. J Clin Invest 1995; 96: 456–464.
- 15 Bergey EJ, Cho MI, Hammarskjold ML, Rekosh D, Levine MJ. Aggregation of human immunodeficiency virus type 1 by human salivary secretions. Crit Rev Oral Biol Medical 1993; 4: 467–474.
- 16 Bergey EJ, Cho MI, Blumberg BM, Hammerskjold MJ, Rekosh D, Epstein LG, Levine MJ. Interaction of HIV-1 and human salivary mucins. J Acq Immune Def Syndr 1994; 7: 995–1002.
- 17 Robinovitch MR, Iversen JM, Resneck L. Anti-infectivity activity of human salivary secretions toward human immunodeficiency virus. Crit Rev Oral Biol Medical 1993; 4: 455–459.
- 18 Veerman ECI, Van Den Keybus PAM, Vissink A, Nieuw Amerongen AV. Human glandular salivas: their separate collection and analysis. Eur J Oral Sci 1996; 104: 346–352.
- 19 Autiero M, Abrescia P, Guardiola J. Interaction of seminal plasma proteins with cell surface antigens: presence of a CD4-binding glycoprotein in human seminal plasma. Exp Cell Res 1991; 197: 268–271.
- 20 Swart PJ, Kuipers EM, Smit C, Van Der Strate BWA, Harmsen MC, Meijer DKF. Lactoferrin – antiviral activity of lactoferrin. Adv Lactoferrin Res 1998; 443: 205–213.
- 21 Veerman ECI, Valentijn-Benz, Van Den Keijbus PAM, Rathman WM, Sheehan JK, Nieuw Amerongen AV. Immunochemical analysis of high molecular-weight human salivary mucins (MG1) using monoclonal antibodies. Arch Oral Biol 1991; 36: 923–932.
- 22 Veerman ECI, Bolscher JGM, Appelmelk BJ, Bloemena E, Van Den Berg TK, Nieuw Amerongen AV. A monoclonal antibody directed against high Mr salivary mucins recognizes the SO3−3Galβ1–3GlcNac moiety of sulfo-Lewisa: a histochemical survey of human and rat tissue. Glycobiology 1997; 7: 37–43.
- 23 Bolscher JGM, Groenink J, Van Der Kwaak JS, Van Der Keijbus PAM, Van ′T Hof W, Veerman ECI, Nieuw Amerongen AV. Detection and quantification of MUC7 in submandibular, sublingual, palatine, and labial saliva by anti-peptide antiserum. J Dent Res 1999; 78: 1362–1369.
- 24 Koot M, Vos AHV, Keet RPM, De Goede REY, Dercksen W, Terpstra FG, Coutinho RA, Miedema F, Tersemette M. HIV-1 biological phenotype in long term infected individuals, evaluated with an MT-2 cocultivation assay. AIDS 1991; 6: 49–54.
- 25 Tersmette M, De Goede REY, Al BJM, Winkel IN, Gruters RA, Cuypers HTM, Huisman HG, Miedema F. Differential syncytium-inducing capacity of human immunodeficiency virus isolates: frequent detection of syncitium-inducing isolates in patients with acquired immunodeficienty syndrome (AIDS) and AIDS-related complex. J Virol 1988; 62: 2026–2032.
- 26 Schuitemaker H, Kootstra NA, Fouchier RA, Hooibrink B, Miedema F. Productive HIV-1 infection of macrophages restricted to the cell fraction with proliferative capacity. EMBO J 1994; 13: 5929–5936.
- 27 Bruisten S, Vangemen B, Koppelman M, Rasch M, Vanstrijp D, Schukkink R, Beyer R, Weigel H, Lens P, Huisman H. Detection of HIV-1 distribution in different blood fractions by 2 nucleic-acid amplification assays. AIDS Res Hum Retrovir 1993; 9: 259–265.
- 28 Bolscher J, Veerman E, Nieuw Amerongen AV, Tulp A, Verwoerd D. Distinct populations of high-Mr mucins secreted by different human salivary glands discriminated by density-gradient electrophoresis. Biochem J 1995; 309: 801–806.
- 29 Patel M, Yanagishita M, Roderiquez G, Bou-Habib DC, Oravecz T, Hascall VC, Norcross MA. Cell surface heparin sulfate proteoglycan mediates HIV-1 infection of cell lines. AIDS Res Hum Retrovir 1993; 9: 167–174.
- 30 Meshcheryakova D, Andreev S, Tarasova S, Sidorova M, Vafina M, Cornilaeva G, Karamov E, Khaitov R. CD4-derived peptide and sulfated polysaccharides have similar mechanisms of anti HIV activity based on electrostatic interactions with positively charged gp120 fragments. Mol Immunol 1993; 30: 993–1001.
- 31 Ligtenberg AJM, Veerman ECI, Nieuw Amerongen AV. A role for Lewis a antigens on salivary agglutinin in binding to Streptococcus mutans. Antonie Van Leeuwenhoek 2000; 77: 21–30.DOI: 10.1023/A:1002054810170
- 32 Krieger M. The other site of scavenger receptors: pattern recognition for host defence. Curr Opin Lipidol 1997; 8: 275–280.
- 33 Iontcheva I, Oppenheim FG, Troxler RF. Human salivay mucin MG1 selectively forms heterotypic complexes with amylase, proline-rich proteins, staterin, and histatins. J Dent Res 1997; 76: 734–743.
- 34 Van-Seunigen I, Houdret N, Hayem A, Davril M. Strong ionic interaction between mucins and two basic proteins, mucus proteinase inhibitor and lysozyme, in human bronchial secretions. Int J Biochem 1992; 24: 303–311.
- 35 McNeely TB, Shugars DC, Rosendahl M, Tucker C, Eisenberg SP, Wahl SM. Inhibition of human immunodeficiency virus type 1 infectivity by secretory leukocyte protease inhibitor occurs prior to reverse transcription. Blood 1997; 90: 1141–1149.
- 36 Crombie R, Silverstein RL, Maclow C, Pierce SFA, Nahchman RL, Laurence J. Identification of a CD36-related thrombospondin 1-binding domain in HIV-1 envelope glycoprotein gp120: relationship to HIV-1specific inhibitory factors in human saliva. J Exp Med 1998; 198: 25–35.
- 37 Nakashima H, Yamamoto N, Masuda M, Fuhii N. Defensins inhibit HIV replication in vitro. AIDS 1993; 7: 1129.
- 38 Baron S, Poast J, Cloyd MW. Why is HIV rarely transmitted by oral secretions? Saliva disrupt orally shed, infected leukocytes. Arch Int Med 1999; 159: 303–310.