title: Human beta-defensins 2 and -3 cointernalize with human immunodeficiency virus via heparan sulfate proteoglycans and reduce infectivity of intracellular virions in tonsil epithelial cells.
abstract: We previously showed that expression of the anti-HIV innate proteins human beta-defensin 2 (hBD2) and hBD3 in adult oral epithelial cells reduces HIV transepithelial transmission by inactivation of virus. However, fetal/infant oral epithelia lack beta-defensin expression, leading to transmission of HIV. The mechanisms of hBD2- and hBD3-mediated HIV inactivation in adult oral epithelial cells are poorly understood. Here we found that heparan sulfate proteoglycans (HSPGs) on the apical surfaces of epithelial cells facilitate simultaneous binding of hBDs and HIV gp120 to the cell surface. HSPG-facilitated binding of hBDs and HIV gp120 to the cell surface did not affect viral attachment. HBD2 or -3 cointernalized with virions in endosomes, formed oligomers, and reduced infectivity of HIV. The anti-HIV effect of combining hBD2 and hBD3 was substantially higher than that of the individual peptides. These findings advance our understanding of the mechanisms of anti-HIV resistance in adult oral epithelium.
authors.affiliation: Department of Medicine, School of Dentistry, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Rossana
authors.initials: R
authors.lastname: Herrera
authors.affiliation: Department of Medicine, School of Dentistry, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Morris
authors.affiliation: Department of Otolaryngology, School of Dentistry, University of California San Francisco, San Francisco, CA, United States.
authors.forename: Kristina
authors.initials: K
authors.lastname: Rosbe
authors.affiliation: Department of Pathology, Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University, Cleveland, OH, United States.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Pathology, Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University, Cleveland, OH, United States.
authors.forename: Aaron
authors.initials: A
authors.lastname: Weinberg
authors.affiliation: Department of Medicine, School of Dentistry, University of California San Francisco, San Francisco, CA, United States; School of Medicine, Department of Orofacial Science, School of Dentistry, University of California San Francisco, San Francisco, CA, United States. Electronic address: sharof.tugizov@ucsf.edu.
authors.forename: Sharof
authors.initials: S
authors.lastname: Tugizov
mesh_terms: D000328:Adult; D045744:Cell Line, Tumor; D002675:Child, Preschool; D011992:Endosomes / Q000276:immunology / Q000821:virology; D004847:Epithelial Cells / Q000166:cytology / Q000821:virology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015658:HIV Infections / Q000635:transmission; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism*; D006367:HeLa Cells; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D007223:Infant; D009092:Mucous Membrane / Q000276:immunology / Q000821:virology; D014066:Palatine Tonsil / Q000166:cytology / Q000821:virology; D011485:Protein Binding; D021381:Protein Transport; D053585:Virus Attachment; D053586:Virus Internalization; D023083:beta-Defensins / Q000276:immunology / Q000378:metabolism*
chemical_list: C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D015699:HIV Envelope Protein gp120; D019812:Heparan Sulfate Proteoglycans; D023083:beta-Defensins; C514793:gp120 protein, Human immunodeficiency virus 1
keywords: Heparan sulfate proteoglycans; Human beta-defensins 2 and -3; Human immunodeficiency virus; Tonsil epithelial cells