title: Heparin increases the infectivity of Human Papillomavirus type 16 independent of cell surface proteoglycans and induces L1 epitope exposure.
abstract: Human Papillomaviruses (HPVs) are the etiological agents of cervical cancer, and HPV-16 is the most prevalent type. Several HPVs require heparan sulfate proteoglycans (HSPGs) for cell binding. Here, we analyse the phenomenon that preincubation of HPV-16 with increasing concentrations of heparin results in partial restoration rather than more efficient inhibition of infection. While corroborating that the HSPGs are cell-binding receptors for HPV-16, heparin-preincubated virus bound to the extracellular matrix (ECM) via laminin-332. Furthermore, the interaction of virions with heparin, a representative of the highly sulfated S-domains of heparan sulfate (HS) chains of HSPGs, allowed HPV-16 infection in the absence of cell surface HSPGs. Therefore, we concluded that specific glycan moieties but not specific HSPG protein backbones are required for infection. The increased binding of an epitope-specific antibody to the viral capsid after heparin binding suggested that initial conformational changes in the HPV-16 virion occur during infection by interaction with'heparin-like' domains of cellular HSPGs. We propose that HS sequences with specific sulfation patterns are required to facilitate HPV-16 infection.
authors.affiliation: Emmy-Noether Group 'Virus Endocytosis', Institutes of Molecular Virology and Medical Biochemistry, University of Münster, Münster, Germany.
authors.forename: Carla
authors.initials: C
authors.lastname: Cerqueira
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Lena
authors.initials: L
authors.lastname: Kühling
authors.forename: Wengang
authors.initials: W
authors.lastname: Chai
authors.forename: Wali
authors.initials: W
authors.lastname: Hafezi
authors.forename: Toin H
authors.initials: TH
authors.lastname: van Kuppevelt
authors.forename: Joachim E
authors.initials: JE
authors.lastname: Kühn
authors.forename: Ten
authors.initials: T
authors.lastname: Feizi
authors.forename: Mario
authors.initials: M
authors.lastname: Schelhaas
mesh_terms: D036022:Capsid Proteins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D000939:Epitopes / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism*; D052162:Human papillomavirus 16 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D011485:Protein Binding; D053585:Virus Attachment / Q000187:drug effects*; D000097794:Kalinin
chemical_list: D036022:Capsid Proteins; D015815:Cell Adhesion Molecules; D000939:Epitopes; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin; D009856:Oncogene Proteins, Viral; D000097794:Kalinin; C063317:L1 protein, Human papillomavirus type 16