Skip to main content
Top
Published in: Virology Journal 1/2008

Open Access 01-12-2008 | Research

The inhibition of the Human Immunodeficiency Virus type 1 activity by crude and purified human pregnancy plug mucus and mucins in an inhibition assay

Authors: Habtom H Habte, Corena de Beer, Zoë E Lotz, Marilyn G Tyler, Leann Schoeman, Delawir Kahn, Anwar S Mall

Published in: Virology Journal | Issue 1/2008

Login to get access

Abstract

Background

The female reproductive tract is amongst the main routes for Human Immunodeficiency Virus (HIV) transmission. Cervical mucus however is known to protect the female reproductive tract from bacterial invasion and fluid loss and regulates and facilitates sperm transport to the upper reproductive tract. The purpose of this study was to purify and characterize pregnancy plug mucins and determine their anti-HIV-1 activity in an HIV inhibition assay.

Methods

Pregnancy plug mucins were purified by caesium chloride density-gradient ultra-centrifugation and characterized by Western blotting analysis. The anti-HIV-1 activities of the crude pregnancy plug mucus and purified pregnancy plug mucins was determined by incubating them with HIV-1 prior to infection of the human T lymphoblastoid cell line (CEM SS cells).

Results

The pregnancy plug mucus had MUC1, MUC2, MUC5AC and MUC5B. The HIV inhibition assay revealed that while the purified pregnancy plug mucins inhibit HIV-1 activity by approximately 97.5%, the crude pregnancy plug mucus failed to inhibit HIV-1 activity.

Conclusion

Although it is not clear why the crude sample did not inhibit HIV-1 activity, it may be that the amount of mucins in the crude pregnancy plug mucus (which contains water, mucins, lipids, nucleic acids, lactoferrin, lysozyme, immunoglobulins and ions), is insufficient to cause viral inhibition or aggregation.
Appendix
Available only for authorised users
Literature
1.
go back to reference Carlstedt I, Sheehan J, Ulmsten U, Wingerup L: Isolation and purification of the mucin component of human cervical mucus. Adv Exp Med Biol 1982, 144: 273-275.CrossRefPubMed Carlstedt I, Sheehan J, Ulmsten U, Wingerup L: Isolation and purification of the mucin component of human cervical mucus. Adv Exp Med Biol 1982, 144: 273-275.CrossRefPubMed
2.
go back to reference Carlstedt I, Lindgren H, Sheehan JK, Ulmsten U, Wingerup L: Isolation and characterization of human cervical-mucus glycoproteins. Biochem J 1983, 211: 13-22.PubMedCentralCrossRefPubMed Carlstedt I, Lindgren H, Sheehan JK, Ulmsten U, Wingerup L: Isolation and characterization of human cervical-mucus glycoproteins. Biochem J 1983, 211: 13-22.PubMedCentralCrossRefPubMed
3.
go back to reference Gipson IK, Spurr-Michaud SJ, Tisdale AS, Kublin C, Cintron C, Keutmann H: Stratified squamous epithelia produce mucin-like glycoproteins. Tissue Cell 1995, 4: 397-404. 10.1016/S0040-8166(95)80060-3CrossRef Gipson IK, Spurr-Michaud SJ, Tisdale AS, Kublin C, Cintron C, Keutmann H: Stratified squamous epithelia produce mucin-like glycoproteins. Tissue Cell 1995, 4: 397-404. 10.1016/S0040-8166(95)80060-3CrossRef
4.
go back to reference Idris N, Carraway KL: Sialomucin complex (MUC4) expression in the rat female reproductive tract. Biol Reprod 1999, 61: 1431-1438. 10.1095/biolreprod61.6.1431CrossRefPubMed Idris N, Carraway KL: Sialomucin complex (MUC4) expression in the rat female reproductive tract. Biol Reprod 1999, 61: 1431-1438. 10.1095/biolreprod61.6.1431CrossRefPubMed
5.
go back to reference Venegas MF, Navas EL, Gaffney RA, Duncan JL, Anderson BE, Schaeffer AJ: Binding of type 1-piliated Escherichia coli to vaginal mucus. Infect Immun 1995, 63: 416-422.PubMedCentralPubMed Venegas MF, Navas EL, Gaffney RA, Duncan JL, Anderson BE, Schaeffer AJ: Binding of type 1-piliated Escherichia coli to vaginal mucus. Infect Immun 1995, 63: 416-422.PubMedCentralPubMed
6.
go back to reference Gipson IK, Ho SB, Spurr-Michaud SJ, Tisdale AS, Zhan Q, Torlakovic E, Pudney J, Anderson DJ, Toribara NW, Hill JA: Mucin genes expressed by human female reproductive tract epithelia. Biol Reprod 1997, 56: 999-1011. 10.1095/biolreprod56.4.999CrossRefPubMed Gipson IK, Ho SB, Spurr-Michaud SJ, Tisdale AS, Zhan Q, Torlakovic E, Pudney J, Anderson DJ, Toribara NW, Hill JA: Mucin genes expressed by human female reproductive tract epithelia. Biol Reprod 1997, 56: 999-1011. 10.1095/biolreprod56.4.999CrossRefPubMed
7.
go back to reference Wiggins R, Hicks SJ, Soothill PW, Millar MR, Corfield AP: Mucinases and sialidases: their role in the pathogenesis of sexually transmitted infections in the female genital tract. Sex Transm Infect 2001, 77: 402-408. 10.1136/sti.77.6.402PubMedCentralCrossRefPubMed Wiggins R, Hicks SJ, Soothill PW, Millar MR, Corfield AP: Mucinases and sialidases: their role in the pathogenesis of sexually transmitted infections in the female genital tract. Sex Transm Infect 2001, 77: 402-408. 10.1136/sti.77.6.402PubMedCentralCrossRefPubMed
8.
go back to reference Argüeso P, Spurr-Michaud S, Tisdale A, Gipson IK: Variation in the amount of T antigen and N-acetyllactosamine oligosaccharides in human cervical mucus secretions with the menstrual cycle. J Clin Endocrinol Metab 2002, 87: 5641-5648. 10.1210/jc.2002-020766CrossRefPubMed Argüeso P, Spurr-Michaud S, Tisdale A, Gipson IK: Variation in the amount of T antigen and N-acetyllactosamine oligosaccharides in human cervical mucus secretions with the menstrual cycle. J Clin Endocrinol Metab 2002, 87: 5641-5648. 10.1210/jc.2002-020766CrossRefPubMed
9.
go back to reference Bergey EJ, Cho MI, Blumberg BM, Hammarskjold ML, Rekosh D, Epstein LG, Levine MJ: Interaction of HIV-1 and human salivary mucins. J Acquir Immune Defic Syndr 1994, 7: 995-1002.PubMed Bergey EJ, Cho MI, Blumberg BM, Hammarskjold ML, Rekosh D, Epstein LG, Levine MJ: Interaction of HIV-1 and human salivary mucins. J Acquir Immune Defic Syndr 1994, 7: 995-1002.PubMed
10.
go back to reference Nagashunmugam T, Friedman HM, Davis C, Kennedy S, Goldstein LT, Malamud D: Human submandibular saliva specifically inhibits HIV type 1. AIDS Res Hum Retroviruses 1997, 13: 371-376.CrossRefPubMed Nagashunmugam T, Friedman HM, Davis C, Kennedy S, Goldstein LT, Malamud D: Human submandibular saliva specifically inhibits HIV type 1. AIDS Res Hum Retroviruses 1997, 13: 371-376.CrossRefPubMed
11.
go back to reference Habte HH, Mall AS, de Beer C, Lotz ZE, Kahn D: The role of crude human saliva and purified salivary MUC5B and MUC7 mucins in the inhibition of Human Immunodeficiency Virus type 1 in an inhibition assay. Virol J 2006, 3: 99. 10.1186/1743-422X-3-99PubMedCentralCrossRefPubMed Habte HH, Mall AS, de Beer C, Lotz ZE, Kahn D: The role of crude human saliva and purified salivary MUC5B and MUC7 mucins in the inhibition of Human Immunodeficiency Virus type 1 in an inhibition assay. Virol J 2006, 3: 99. 10.1186/1743-422X-3-99PubMedCentralCrossRefPubMed
12.
go back to reference Habte HH, de Beer C, Lotz ZE, Tyler MG, Kahn D, Mall AS: Inhibition of Human Immunodeficiency Virus type 1 activity by purified human breast milk mucin (MUC1) in an inhibition assay. Neonatology 2008,93(3):162-170. 10.1159/000108414CrossRefPubMed Habte HH, de Beer C, Lotz ZE, Tyler MG, Kahn D, Mall AS: Inhibition of Human Immunodeficiency Virus type 1 activity by purified human breast milk mucin (MUC1) in an inhibition assay. Neonatology 2008,93(3):162-170. 10.1159/000108414CrossRefPubMed
13.
go back to reference Habte HH, Lotz ZE, Tyler MG, Abrahams M, Rodriques J, Kahn D, Kotwal GJ, Mall AS: Anti viral activity of purified human breast milk mucin. Neonatology 2007, 92: 96-104. 10.1159/000100808CrossRefPubMed Habte HH, Lotz ZE, Tyler MG, Abrahams M, Rodriques J, Kahn D, Kotwal GJ, Mall AS: Anti viral activity of purified human breast milk mucin. Neonatology 2007, 92: 96-104. 10.1159/000100808CrossRefPubMed
14.
go back to reference Eriksen GV, Carlstedt I, Uldbjerg N, Ernst E: Cervical mucins affect the mobility of human spermatozoa in vitro . Fertil Steril 1998, 70: 350-354. 10.1016/S0015-0282(98)00158-7CrossRefPubMed Eriksen GV, Carlstedt I, Uldbjerg N, Ernst E: Cervical mucins affect the mobility of human spermatozoa in vitro . Fertil Steril 1998, 70: 350-354. 10.1016/S0015-0282(98)00158-7CrossRefPubMed
15.
go back to reference Losina E, Anglaret X, Yazdanpanah Y, Wang B, Toure S, Seage GR III, N'Dri-Yoman T, Walensky RP, Dakoury-Dogbo N, Goldie SJ, Messou E, Weinstein MC, Deuffic-Burban S, Salamon R, Freedberg KA: Impact of opportunistic diseases on chronic mortality in HIV-infected adults in Côte d' Ivoire. S Afr Med J 2006, 96: 526-529.PubMed Losina E, Anglaret X, Yazdanpanah Y, Wang B, Toure S, Seage GR III, N'Dri-Yoman T, Walensky RP, Dakoury-Dogbo N, Goldie SJ, Messou E, Weinstein MC, Deuffic-Burban S, Salamon R, Freedberg KA: Impact of opportunistic diseases on chronic mortality in HIV-infected adults in Côte d' Ivoire. S Afr Med J 2006, 96: 526-529.PubMed
16.
go back to reference Shaikh N, Abdullah F, Lombard CJ, Smit L, Bradshaw D, Makubalo L: Masking through averages-intraprovincial heterogeneity in HIV prevalence within the Western Cape. S Afr Med J 2006, 96: 538-543.PubMed Shaikh N, Abdullah F, Lombard CJ, Smit L, Bradshaw D, Makubalo L: Masking through averages-intraprovincial heterogeneity in HIV prevalence within the Western Cape. S Afr Med J 2006, 96: 538-543.PubMed
17.
go back to reference Strode A, Slack C, Mushariwa M: HIV vaccine research-south Africa's ethical-legal framework and its ability to promote the welfare of trial participants. S Afr Med J 2005, 95: 598-601.PubMed Strode A, Slack C, Mushariwa M: HIV vaccine research-south Africa's ethical-legal framework and its ability to promote the welfare of trial participants. S Afr Med J 2005, 95: 598-601.PubMed
18.
go back to reference Kagee A, Toefy Y, Simbayi L, Kalichman S: HIV prevalence in three predominantly Muslim residential areas in the Cape Town metropole. S Afr Med J 2005, 95: 512-516.PubMed Kagee A, Toefy Y, Simbayi L, Kalichman S: HIV prevalence in three predominantly Muslim residential areas in the Cape Town metropole. S Afr Med J 2005, 95: 512-516.PubMed
19.
go back to reference Govender U: The biochemical and molecular characterization of respiratory mucins in TB. In MSc thesis. University of Cape Town, Surgery Department; 2006. Govender U: The biochemical and molecular characterization of respiratory mucins in TB. In MSc thesis. University of Cape Town, Surgery Department; 2006.
20.
go back to reference Chirwa N, Tyler M, Govender D, Kavin B, Goldberg P, Krige J, Lotz Z, Alistair H, Kahn D, Mall A: The biochemical and immunohistochemical characterisation of mucins in colonic disease. A pilot study. S Afr J Surg 2007, 45: 18-23.PubMed Chirwa N, Tyler M, Govender D, Kavin B, Goldberg P, Krige J, Lotz Z, Alistair H, Kahn D, Mall A: The biochemical and immunohistochemical characterisation of mucins in colonic disease. A pilot study. S Afr J Surg 2007, 45: 18-23.PubMed
21.
go back to reference Malamud D, Davis C, Berthold P, Roth E, Friedman H: Human submandibular saliva aggregates HIV. AIDS Res Hum Retroviruses 1993, 9: 633-637.CrossRefPubMed Malamud D, Davis C, Berthold P, Roth E, Friedman H: Human submandibular saliva aggregates HIV. AIDS Res Hum Retroviruses 1993, 9: 633-637.CrossRefPubMed
22.
go back to reference Malamud D, Nagashunmugam T, Davis C, Kennedy S, Abrams WR, Kream R, Friedman HM: Inhibition of HIV infectivity by human saliva. Oral Dis 1997, (Suppl 3):58-63. Malamud D, Nagashunmugam T, Davis C, Kennedy S, Abrams WR, Kream R, Friedman HM: Inhibition of HIV infectivity by human saliva. Oral Dis 1997, (Suppl 3):58-63.
23.
go back to reference Gipson IK, Moccia R, Spurr-Michaud SJ, Argüeso P, Gargiulo AR, Hill JA, Offner GD, Keutmann HT: The amount of MUC5B mucin in cervical mucus peaks at midcycle. J Clin Endocrinol Metab 2001, 86: 594-600. 10.1210/jc.86.2.594PubMed Gipson IK, Moccia R, Spurr-Michaud SJ, Argüeso P, Gargiulo AR, Hill JA, Offner GD, Keutmann HT: The amount of MUC5B mucin in cervical mucus peaks at midcycle. J Clin Endocrinol Metab 2001, 86: 594-600. 10.1210/jc.86.2.594PubMed
24.
go back to reference Archibald DW, Cole GA: In vitro inhibition of HIV-1 infectivity by human salivas. AIDS Res Hum Retroviruses 1990, 6: 1425-1432.CrossRefPubMed Archibald DW, Cole GA: In vitro inhibition of HIV-1 infectivity by human salivas. AIDS Res Hum Retroviruses 1990, 6: 1425-1432.CrossRefPubMed
25.
go back to reference Shugars DC, Alexander AL, Fu K, Freel SA: Endogenous salivary inhibitors of human immunodeficiency virus. Arch Oral Biol 1999, 44: 445-453. 10.1016/S0003-9969(99)00003-5CrossRefPubMed Shugars DC, Alexander AL, Fu K, Freel SA: Endogenous salivary inhibitors of human immunodeficiency virus. Arch Oral Biol 1999, 44: 445-453. 10.1016/S0003-9969(99)00003-5CrossRefPubMed
26.
go back to reference Shugars DC, Wahl SM: The role of the oral environment in HIV-1 transmission. J Am Dent Assoc 1998, 129: 851-858.CrossRefPubMed Shugars DC, Wahl SM: The role of the oral environment in HIV-1 transmission. J Am Dent Assoc 1998, 129: 851-858.CrossRefPubMed
27.
go back to reference Creeth JM: Constituents of mucus and their separation. Br Med Bull 1978, 34: 17-24.PubMed Creeth JM: Constituents of mucus and their separation. Br Med Bull 1978, 34: 17-24.PubMed
28.
go back to reference Treurnicht FK, Smith TL, Engelbrecht S, Claassen M, Robson BA, Zeier M, van Rensburg EJ: Genotypic and phenotypic analysis of the env gene from South African HIV-1 subtype B and C isolates. J Med Virol 2002, 68: 141-146. 10.1002/jmv.10199CrossRefPubMed Treurnicht FK, Smith TL, Engelbrecht S, Claassen M, Robson BA, Zeier M, van Rensburg EJ: Genotypic and phenotypic analysis of the env gene from South African HIV-1 subtype B and C isolates. J Med Virol 2002, 68: 141-146. 10.1002/jmv.10199CrossRefPubMed
29.
go back to reference Lallos LB, Laal S, Hoxie JA, Zolla-Pazner S, Bandres JC: Exclusion of HIV Coreceptors CXCR4, CCR5 and CCR3 from the HIV envelope. AIDS Res Hum Retroviruses 1999, 15: 895-897. 10.1089/088922299310601CrossRefPubMed Lallos LB, Laal S, Hoxie JA, Zolla-Pazner S, Bandres JC: Exclusion of HIV Coreceptors CXCR4, CCR5 and CCR3 from the HIV envelope. AIDS Res Hum Retroviruses 1999, 15: 895-897. 10.1089/088922299310601CrossRefPubMed
30.
go back to reference Nara PL, Hatch WC, Dunlop NM, Robey WG, Arthur LO, Gonda MA, Fischinger PJ: Simple, rapid, quantitative, syncytium-forming microassay for the detection of human immunodeficiency virus neutralizing antibody. AIDS Res Hum Retroviruses 1987, 3: 283-302.CrossRefPubMed Nara PL, Hatch WC, Dunlop NM, Robey WG, Arthur LO, Gonda MA, Fischinger PJ: Simple, rapid, quantitative, syncytium-forming microassay for the detection of human immunodeficiency virus neutralizing antibody. AIDS Res Hum Retroviruses 1987, 3: 283-302.CrossRefPubMed
31.
go back to reference Creeth JM, Denborough MA: The use of equilibrium-density-gradient methods for the preparation and characterization of blood-group-specific glycoproteins. Biochem J 1970, 117: 879-91.PubMedCentralCrossRefPubMed Creeth JM, Denborough MA: The use of equilibrium-density-gradient methods for the preparation and characterization of blood-group-specific glycoproteins. Biochem J 1970, 117: 879-91.PubMedCentralCrossRefPubMed
32.
go back to reference Mall AS: Gastro-duodenal mucin isolation and structure. PhD thesis. University of Newcastle upon Tyne, Department of Physiological Sciences; 1988. Mall AS: Gastro-duodenal mucin isolation and structure. PhD thesis. University of Newcastle upon Tyne, Department of Physiological Sciences; 1988.
33.
go back to reference Francis RD, Bradford HB: Some biological and physical properties of molluscum contagiosum virus propagated in cell culture. J Virol 1976, 19: 382-388.PubMedCentralPubMed Francis RD, Bradford HB: Some biological and physical properties of molluscum contagiosum virus propagated in cell culture. J Virol 1976, 19: 382-388.PubMedCentralPubMed
34.
go back to reference Wickstrom C, Davies JR, Eriksen GV, Veerman ECI, Carlstedt I: MUC5B is a major gel forming, oligomeric mucin from human salivary glands, respiratory tract and endocervix: identification of glycoforms and C-terminal cleavage. Biochem J 1998, 334: 685-693.PubMedCentralCrossRefPubMed Wickstrom C, Davies JR, Eriksen GV, Veerman ECI, Carlstedt I: MUC5B is a major gel forming, oligomeric mucin from human salivary glands, respiratory tract and endocervix: identification of glycoforms and C-terminal cleavage. Biochem J 1998, 334: 685-693.PubMedCentralCrossRefPubMed
35.
go back to reference Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970, 227: 680-685. 10.1038/227680a0CrossRefPubMed Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970, 227: 680-685. 10.1038/227680a0CrossRefPubMed
36.
go back to reference Thornton DJ, Khan N, Mehrotra R, Howard M, Veerman E, Packer NH, Sheehan JK: Salivary mucin MG1 is comprised almost entirely of different glycosylated forms of the MUC5B gene product. Glycobiology 1999, 9: 293-302. 10.1093/glycob/9.3.293CrossRefPubMed Thornton DJ, Khan N, Mehrotra R, Howard M, Veerman E, Packer NH, Sheehan JK: Salivary mucin MG1 is comprised almost entirely of different glycosylated forms of the MUC5B gene product. Glycobiology 1999, 9: 293-302. 10.1093/glycob/9.3.293CrossRefPubMed
37.
go back to reference Mantle M, Allen A: A colorimetric assay for glycoproteins based on the periodic acid/Schiff stain [proceedings]. Biochem Soc Trans 1978, 6: 607-609.CrossRefPubMed Mantle M, Allen A: A colorimetric assay for glycoproteins based on the periodic acid/Schiff stain [proceedings]. Biochem Soc Trans 1978, 6: 607-609.CrossRefPubMed
38.
go back to reference Lowry OH, Rosebrough NJ, Farr L, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 1951, 193: 265-275.PubMed Lowry OH, Rosebrough NJ, Farr L, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 1951, 193: 265-275.PubMed
Metadata
Title
The inhibition of the Human Immunodeficiency Virus type 1 activity by crude and purified human pregnancy plug mucus and mucins in an inhibition assay
Authors
Habtom H Habte
Corena de Beer
Zoë E Lotz
Marilyn G Tyler
Leann Schoeman
Delawir Kahn
Anwar S Mall
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2008
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-5-59

Other articles of this Issue 1/2008

Virology Journal 1/2008 Go to the issue