The VPS4 component of the ESCRT machinery plays an essential role in HPV infectious entry and capsid disassembly.

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dc.creatorBroniarczyk, Justyna
dc.creatorPim, David
dc.creatorMassimi, Paola
dc.creatorBergant, Martina
dc.creatorGoździcka-Józefiak, Anna
dc.creatorCrump, Colin
dc.creatorBanks, Lawrence
dc.date2018-08-15T15:30:08Z
dc.date2018-08-15T15:30:08Z
dc.date2017-03-28
dc.date.accessioned2026-08-03T01:32:51Z
dc.descriptionHuman Papillomavirus (HPV) infection involves multiple steps, from cell attachment, through endocytic trafficking towards the trans-Golgi network, and, ultimately, the entry into the nucleus during mitosis. An essential viral protein in infectious entry is the minor capsid protein L2, which engages different components of the endocytic sorting machinery during this process. The ESCRT machinery is one such component that seems to play an important role in the early stages of infection. Here we have analysed the role of specific ESCRT components in HPV infection, and we find an essential role for VPS4. Loss of VPS4 blocks infection with multiple PV types, suggesting an evolutionarily conserved critical step in infectious entry. Intriguingly, both L1 and L2 can interact with VPS4, and appear to be in complex with VPS4 during the early stages of virus infection. By using cell lines stably expressing a dominant-negative mutant form of VPS4, we also show that loss of VPS4 ATPase activity results in a marked delay in capsid uncoating, resulting in a defect in the endocytic transport of incoming PsVs. These results demonstrate that the ESCRT machinery, and in particular VPS4, plays a critical role in the early stages of PV infection.
dc.formatElectronic
dc.formatapplication/pdf
dc.identifier2045-2322
dc.identifierhttps://www.repository.cam.ac.uk/handle/1810/278851
dc.identifier10.17863/CAM.26228
dc.identifier2045-2322
dc.identifier.urihttps://repo.dare.co.zw/handle/123456789/155630
dc.languageeng
dc.languageeng
dc.publisherSpringer Nature
dc.publisherhttps://doi.org/10.1038/srep45159
dc.rightsAttribution 4.0 International
dc.rightshttp://creativecommons.org/licenses/by/4.0/
dc.subjectATPases Associated with Diverse Cellular Activities
dc.subjectCapsid Proteins
dc.subjectCell Line
dc.subjectCells, Cultured
dc.subjectEndosomal Sorting Complexes Required for Transport
dc.subjectHumans
dc.subjectPapillomaviridae
dc.subjectPapillomavirus Infections
dc.subjectProtein Binding
dc.subjectProtein Transport
dc.subjectVacuolar Proton-Translocating ATPases
dc.subjectViral Proteins
dc.subjectVirus Internalization
dc.subjectVirus Uncoating
dc.titleThe VPS4 component of the ESCRT machinery plays an essential role in HPV infectious entry and capsid disassembly.
dc.typeArticle

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