Publication
Title
Lamin B1 curtails early human papillomavirus infection by safeguarding nuclear compartmentalization and autophagic capacity
Author
Abstract
Human papillomavirus (HPV) infection is a primary cause of cervical and head-and-neck cancers. The HPV genome enters the nucleus during mitosis when the nuclear envelope disassembles. Given that lamins maintain nuclear integrity during interphase, we asked to what extent their loss would affect early HPV infection. To address this question, we infected human cervical cancer cells and keratinocytes lacking the major lamins with a HPV16 pseudovirus (HP-PsV) encoding an EGFP reporter. We found that a sustained reduction or complete loss of lamin B1 significantly increased HP-PsV infection rate. A corresponding greater nuclear HP-PsV load in LMNB1 knockout cells was directly related to their prolonged mitotic window and extensive nuclear rupture propensity. Despite the increased HP-PsV presence, EGFP transcript levels remained virtually unchanged, indicating an additional defect in protein turnover. Further investigation revealed that LMNB1 knockout led to a substantial decrease in autophagic capacity, possibly linked to the persistent activation of cGAS by cytoplasmic chromatin exposure. Thus, the attrition of lamin B1 increases nuclear perviousness and attenuates autophagic capacity, creating an environment conducive to unrestrained accumulation of HPV capsids. Our identification of lower lamin B1 levels and nuclear BAF foci in the basal epithelial layer of several human cervix samples suggests that this pathway may contribute to an increased individual susceptibility to HPV infection.
Language
English
Source (journal)
Cellular and molecular life sciences. - Basel, 1997, currens
Publication
Basel : 2024
ISSN
1420-682X [print]
1420-9071 [online]
DOI
10.1007/S00018-024-05194-3
Volume/pages
81 :1 (2024) , p. 1-16
Article Reference
141
Full text (Publisher's DOI)
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UAntwerpen
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Publications with a UAntwerp address
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Creation 15.03.2024
Last edited 16.03.2024
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