Authors:	Schweiger, Linda Lelieveld-Fast, Laura A. Mikuličić, Snježana Strunk, Johannes Freitag, Kirsten Tenzer, Stefan Clement, Albrecht M. Florin, Luise
Title:	HPV16 induces formation of virus-p62-PML hybrid bodies to enable infection
Online publication date:	20-Jan-2023
Year of first publication:	2022
Language:	english
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
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8595
Version:	Published version
Publication type:	Zeitschriftenaufsatz
Document type specification:	Scientific article
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Viruses 14 7
Pages or article number:	1478
Publisher:	MDPI
Publisher place:	Basel
Issue date:	2022
ISSN:	1999-4915
Publisher DOI:	10.3390/v14071478
Appears in collections:	DFG-491381577-G