| Autor: |
Freya Molenberghs, Marlies Verschuuren, Lauran Vandeweyer, Sarah Peeters, Johannes Bogers, Claudina Perez Novo, Wim Vanden Berghe, Hans De Reu, Nathalie Cools, Mario Schelhaas, Winnok De Vos |
| Rok vydání: |
2022 |
| DOI: |
10.21203/rs.3.rs-1911728/v1 |
| Popis: |
Human papillomavirus (HPV) infection is the prime elicitor of cervical and head-and-neck cancers. The HPV genome enters the nucleus during mitosis when the nuclear envelope dismantles. Since lamins safeguard nuclear integrity during interphase, we asked to what extent their loss would affect early HPV infection. We challenged human cervical cancer cells knocked out for the major lamin genes with a HPV16 pseudovirus (PsV) encoding an EGFP reporter and found that loss of lamin B1 amplified infection rate. A prolonged mitotic window and extensive nuclear rupture propensity during interphase led to a higher nuclear PsV load in LMNB1 knockout cells, but unchanged EGFP transcript levels pointed to an additional defect in protein turnover. We found a strong decrease in autophagic capacity in LMNB1 knockout cells, which we connect to the persistent activation of cGAS. Thus, loss of lamin B1 increases nuclear perviousness and blunts the autophagic capacity, which primes cells for unrestrained buildup of HPV capsids. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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