Gutenberg Open Science: HPV16 induces formation of virus-p62-PML hybrid bodies to enable infection

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-8595

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DC Field	Value	Language
dc.contributor.author	Schweiger, Linda	-
dc.contributor.author	Lelieveld-Fast, Laura A.	-
dc.contributor.author	Mikuličić, Snježana	-
dc.contributor.author	Strunk, Johannes	-
dc.contributor.author	Freitag, Kirsten	-
dc.contributor.author	Tenzer, Stefan	-
dc.contributor.author	Clement, Albrecht M.	-
dc.contributor.author	Florin, Luise	-
dc.date.accessioned	2023-01-20T08:22:39Z	-
dc.date.available	2023-01-20T08:22:39Z	-
dc.date.issued	2022	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/8611	-
dc.description.abstract	Human papillomaviruses (HPVs) inflict a significant burden on the human population. The clinical manifestations caused by high-risk HPV types are cancers at anogenital sites, including cervical cancer, as well as head and neck cancers. Host cell defense mechanisms such as autophagy are initiated upon HPV entry. At the same time, the virus modulates cellular antiviral processes and structures such as promyelocytic leukemia nuclear bodies (PML NBs) to enable infection. Here, we uncover the autophagy adaptor p62, also known as p62/sequestosome-1, as a novel proviral factor in infections by the high-risk HPV type 16 (HPV16). Proteomics, imaging and interaction studies of HPV16 pseudovirus-treated HeLa cells display that p62 is recruited to virus-filled endosomes, interacts with incoming capsids, and accompanies the virus to PML NBs, the sites of viral transcription and replication. Cellular depletion of p62 significantly decreased the delivery of HPV16 viral DNA to PML NBs and HPV16 infection rate. Moreover, the absence of p62 leads to an increase in the targeting of viral components to autophagic structures and enhanced degradation of the viral capsid protein L2. The proviral role of p62 and formation of virus-p62-PML hybrid bodies have also been observed in human primary keratinocytes, the HPV target cells. Together, these findings suggest the previously unrecognized virus-induced formation of p62-PML hybrid bodies as a viral mechanism to subvert the cellular antiviral defense, thus enabling viral gene expression. Keywords: human papillomavirus; HPV16; L2; p62; sequestosome-1; autophagy; antiviral defense; promyelocytic leukemia nuclear bodies (PML NB); hybrid bodies	en_GB
dc.description.sponsorship	Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 491381577	de
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	HPV16 induces formation of virus-p62-PML hybrid bodies to enable infection	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-8595	-
jgu.type.contenttype	Scientific article	de
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.number	2700	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	Viruses	de
jgu.journal.volume	14	de
jgu.journal.issue	7	de
jgu.pages.alternative	1478	de
jgu.publisher.year	2022	-
jgu.publisher.name	MDPI	de
jgu.publisher.place	Basel	de
jgu.publisher.issn	1999-4915	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	610	de
jgu.publisher.doi	10.3390/v14071478	de
jgu.organisation.ror	https://ror.org/023b0x485	-
jgu.subject.dfg	Lebenswissenschaften	de
Appears in collections:	DFG-491381577-G

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