Heparin increases the infectivity of Human Papillomavirus Type 16 independent of cell surface proteoglycans and induces L1 epitope exposure |
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| Authors: | Carla Cerqueira Yan Liu Lena Kühling Wengang Chai Wali Hafezi Toin H. van Kuppevelt Joachim E. Kühn Ten Feizi Mario Schelhaas |
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| Affiliation: | 1. Emmy‐Noether Group ‘Virus Endocytosis’, Institutes of Molecular Virology and Medical Biochemistry, University of Münster, , Münster, Germany;2. Glycosciences Laboratory, Imperial College London, , London, UK;3. University Hospital Münster, Institute of Medical Microbiology – Clinical Virology, , Münster, Germany;4. Department of Biochemistry, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, , Nijmegen, The Netherlands |
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| 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. |
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