The VPS4 component of the ESCRT machinery plays an essential role in HPV infectious entry and capsid disassembly.
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Authors
Broniarczyk, Justyna
Pim, David
Massimi, Paola
Bergant, Martina
Goździcka-Józefiak, Anna
Banks, Lawrence
Publication Date
2017-03-28Journal Title
Scientific reports
ISSN
2045-2322
Volume
7
Pages
45159
Language
eng
Type
Article
This Version
VoR
Physical Medium
Electronic
Metadata
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Broniarczyk, J., Pim, D., Massimi, P., Bergant, M., Goździcka-Józefiak, A., Crump, C., & Banks, L. (2017). The VPS4 component of the ESCRT machinery plays an essential role in HPV infectious entry and capsid disassembly.. Scientific reports, 7 45159. https://doi.org/10.1038/srep45159
Abstract
Human Papillomavirus (HPV) infection involves multiple steps, from cell attachment, through endocytic tra cking 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 di erent 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 speci c ESCRT components in HPV infection, and we nd 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.
Keywords
Cells, Cultured, Cell Line, Humans, Papillomaviridae, Papillomavirus Infections, Vacuolar Proton-Translocating ATPases, Viral Proteins, Capsid Proteins, Protein Binding, Protein Transport, Virus Internalization, Endosomal Sorting Complexes Required for Transport, Virus Uncoating, ATPases Associated with Diverse Cellular Activities
Identifiers
External DOI: https://doi.org/10.1038/srep45159
This record's URL: https://www.repository.cam.ac.uk/handle/1810/278851
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