title: The VPS4 component of the ESCRT machinery plays an essential role in HPV infectious entry and capsid disassembly.
abstract: Human 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.
authors.affiliation: Tumour Virology Laboratory, International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste, I-34149, Italy.|Department of Molecular Virology, Adam Mickiewicz University, Umultowska 89, Poznan, 61-614, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Broniarczyk
authors.affiliation: Tumour Virology Laboratory, International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste, I-34149, Italy.
authors.forename: David
authors.initials: D
authors.lastname: Pim
authors.affiliation: Tumour Virology Laboratory, International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste, I-34149, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Massimi
authors.affiliation: Centre for Biomedical Sciences and Engineering, University of Nova Gorica, Vipava, Slovenia.
authors.forename: Martina
authors.initials: M
authors.lastname: Bergant
authors.affiliation: Department of Molecular Virology, Adam Mickiewicz University, Umultowska 89, Poznan, 61-614, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Goździcka-Józefiak
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.
authors.forename: Colin
authors.initials: C
authors.lastname: Crump
authors.affiliation: Tumour Virology Laboratory, International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste, I-34149, Italy.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Banks
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities / Q000378:metabolism*; D036022:Capsid Proteins / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D006801:Humans; D027383:Papillomaviridae / Q000502:physiology*; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000821:virology*; D011485:Protein Binding; D021381:Protein Transport; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism; D053586:Virus Internalization; D057646:Virus Uncoating
chemical_list: D036022:Capsid Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D014764:Viral Proteins; D025262:Vacuolar Proton-Translocating ATPases; D000074183:ATPases Associated with Diverse Cellular Activities; C490305:VPS4A protein, human