title: Binding of human papillomavirus type 16 to heparan sulfate is inhibited by mucosal antibodies from patients with low-grade squamous intraepithelial lesions but not from cervical cancer patients.
abstract: Mucosal antibodies against human papillomavirus type 16 (HPV16) capsids have been detected in infected women. To determine whether these antibodies recognize and block the receptor site mediating attachment of HPV16 to heparan sulfate, mucus samples from 126 HPV16-associated low-grade squamous intraepithelial lesion (LSIL) and 85 cervical cancer patients, previously found to react to HPV16 virus-like particles (VLP), and 101 normal controls were tested in an inhibition assay, using HPV16 VLP and heparan sulfate proteoglycan-coated plates. Inhibition levels of 9.3-67.2% were mediated by type-specific antibodies in 94.4% of LSIL patients. Cervical cancer cases showed significantly lower levels of inhibition than LSIL samples (P < 0.0001). The potential of antibodies to inhibit infection was explored in a pseudoinfection system using HPV16 pseudovirions. Inhibition of pseudoinfection by LSIL samples was significantly higher than that observed in the controls (P < 0.001) and cervical cancer cases (P < 0.005). These results indicate that mucosal antibodies inhibiting binding of VLP to heparan sulfate are developed in most LSIL patients, but are hardly present in cervical cancer patients.
authors.affiliation: Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México.
authors.forename: Tania V
authors.initials: TV
authors.lastname: Lopez
authors.forename: Clotilde
authors.initials: C
authors.lastname: Cancio
authors.forename: Fernando
authors.initials: F
authors.lastname: Cruz-Talonia
authors.forename: Blanca
authors.initials: B
authors.lastname: Ruiz
authors.forename: Martin
authors.initials: M
authors.lastname: Sapp
authors.forename: Leticia
authors.initials: L
authors.lastname: Rocha-Zavaleta
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D005260:Female; D006497:Heparan Sulfate / Q000378:metabolism*; D052162:Human papillomavirus 16 / Q000276:immunology* / Q000378:metabolism; D052161:Human papillomavirus 18 / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D030361:Papillomavirus Infections / Q000276:immunology* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000821:virology; D014626:Vaginal Smears; D014771:Virion / Q000276:immunology / Q000378:metabolism; D002578:Uterine Cervical Dysplasia / Q000276:immunology* / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D006497:Heparan Sulfate; D007070:Immunoglobulin A; D007074:Immunoglobulin G