Exogenous Vimentin Supplementation Transiently Affects Early Steps during HPV16 Pseudovirus Infection

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dc.contributor.authorCarse, Sinead
dc.contributor.authorLang, Dirk
dc.contributor.authorKatz, Arieh A
dc.contributor.authorSchäfer, Georgia
dc.date.accessioned2022-04-04T09:52:15Z
dc.date.available2022-04-04T09:52:15Z
dc.date.issued2021-12-10
dc.date.updated2021-12-23T15:06:39Z
dc.description.abstractUnderstanding and modulating the early steps in oncogenic Human Papillomavirus (HPV) infection has great cancer-preventative potential, as this virus is the etiological agent of virtually all cervical cancer cases and is associated with many other anogenital and oropharyngeal cancers. Previous work from our laboratory has identified cell-surface-expressed vimentin as a novel HPV16 pseudovirus (HPV16-PsVs)-binding molecule modulating its infectious potential. To further explore its mode of inhibiting HPV16-PsVs internalisation, we supplemented it with exogenous recombinant human vimentin and show that only the globular form of the molecule (as opposed to the filamentous form) inhibited HPV16-PsVs internalisation in vitro. Further, this inhibitory effect was only transient and not sustained over prolonged incubation times, as demonstrated in vitro and in vivo, possibly due to full-entry molecule engagement by the virions once saturation levels have been reached. The vimentin-mediated delay of HPV16-PsVs internalisation could be narrowed down to affecting multiple steps during the virus’ interaction with the host cell and was found to affect both heparan sulphate proteoglycan (HSPG) binding as well as the subsequent entry receptor complex engagement. Interestingly, decreased pseudovirus internalisation (but not infection) in the presence of vimentin was also demonstrated for oncogenic HPV types 18, 31 and 45. Together, these data demonstrate the potential of vimentin as a modulator of HPV infection which can be used as a tool to study early mechanisms in infectious internalisation. However, further refinement is needed with regard to vimentin’s stabilisation and formulation before its development as an alternative prophylactic means.en_US
dc.identifierdoi: 10.3390/v13122471
dc.identifier.apacitationCarse, S., Lang, D., Katz, A. A., & Schäfer, G. (2021). Exogenous Vimentin Supplementation Transiently Affects Early Steps during HPV16 Pseudovirus Infection. <i>Viruses</i>, 13(12), 2471. http://hdl.handle.net/11427/36259en_ZA
dc.identifier.chicagocitationCarse, Sinead, Dirk Lang, Arieh A Katz, and Georgia Schäfer "Exogenous Vimentin Supplementation Transiently Affects Early Steps during HPV16 Pseudovirus Infection." <i>Viruses</i> 13, 12. (2021): 2471. http://hdl.handle.net/11427/36259en_ZA
dc.identifier.citationCarse, S., Lang, D., Katz, A.A. & Schäfer, G. 2021. Exogenous Vimentin Supplementation Transiently Affects Early Steps during HPV16 Pseudovirus Infection. <i>Viruses.</i> 13(12):2471. http://hdl.handle.net/11427/36259en_ZA
dc.identifier.ris TY - Journal Article AU - Carse, Sinead AU - Lang, Dirk AU - Katz, Arieh A AU - Schäfer, Georgia AB - Understanding and modulating the early steps in oncogenic Human Papillomavirus (HPV) infection has great cancer-preventative potential, as this virus is the etiological agent of virtually all cervical cancer cases and is associated with many other anogenital and oropharyngeal cancers. Previous work from our laboratory has identified cell-surface-expressed vimentin as a novel HPV16 pseudovirus (HPV16-PsVs)-binding molecule modulating its infectious potential. To further explore its mode of inhibiting HPV16-PsVs internalisation, we supplemented it with exogenous recombinant human vimentin and show that only the globular form of the molecule (as opposed to the filamentous form) inhibited HPV16-PsVs internalisation in vitro. Further, this inhibitory effect was only transient and not sustained over prolonged incubation times, as demonstrated in vitro and in vivo, possibly due to full-entry molecule engagement by the virions once saturation levels have been reached. The vimentin-mediated delay of HPV16-PsVs internalisation could be narrowed down to affecting multiple steps during the virus&rsquo; interaction with the host cell and was found to affect both heparan sulphate proteoglycan (HSPG) binding as well as the subsequent entry receptor complex engagement. Interestingly, decreased pseudovirus internalisation (but not infection) in the presence of vimentin was also demonstrated for oncogenic HPV types 18, 31 and 45. Together, these data demonstrate the potential of vimentin as a modulator of HPV infection which can be used as a tool to study early mechanisms in infectious internalisation. However, further refinement is needed with regard to vimentin&rsquo;s stabilisation and formulation before its development as an alternative prophylactic means. DA - 2021-12-10 DB - OpenUCT DP - University of Cape Town IS - 12 J1 - Viruses KW - Human Papillomavirus KW - HPV KW - vimentin KW - receptor KW - heparan sulphate proteoglycan KW - HSPG LK - https://open.uct.ac.za PY - 2021 T1 - Exogenous Vimentin Supplementation Transiently Affects Early Steps during HPV16 Pseudovirus Infection TI - Exogenous Vimentin Supplementation Transiently Affects Early Steps during HPV16 Pseudovirus Infection UR - http://hdl.handle.net/11427/36259 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/36259
dc.identifier.vancouvercitationCarse S, Lang D, Katz AA, Schäfer G. Exogenous Vimentin Supplementation Transiently Affects Early Steps during HPV16 Pseudovirus Infection. Viruses. 2021;13(12):2471. http://hdl.handle.net/11427/36259.en_ZA
dc.language.isoenen_US
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_US
dc.publisher.facultyFaculty of Health Sciencesen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceVirusesen_US
dc.source.journalissue12en_US
dc.source.journalvolume13en_US
dc.source.pagination2471en_US
dc.source.urihttps://www.mdpi.com/journal/viruses
dc.subjectHuman Papillomavirus
dc.subjectHPV
dc.subjectvimentin
dc.subjectreceptor
dc.subjectheparan sulphate proteoglycan
dc.subjectHSPG
dc.titleExogenous Vimentin Supplementation Transiently Affects Early Steps during HPV16 Pseudovirus Infectionen_US
dc.typeJournal Articleen_US
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