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Lelieveld-Fast, Laura A.
Clement, Albrecht M.
|Title:||HPV16 induces formation of virus-p62-PML hybrid bodies to enable infection|
|Online publication date:||20-Jan-2023|
|Year of first publication:||2022|
|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|
610 Medical sciences
|Institution:||Johannes Gutenberg-Universität Mainz|
|Department:||FB 04 Medizin|
|Document type specification:||Scientific article|
|Information on rights of use:||https://creativecommons.org/licenses/by/4.0/|
|Pages or article number:||1478|
|Appears in collections:||DFG-491381577-G|
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