CRM1 Promotes Capsid Disassembly and Nuclear Envelope Translocation of Adenovirus Independently of Its Export Function.
| dc.rights.license | open | en_US |
| dc.contributor.author | LAGADEC, Floriane | |
| hal.structure.identifier | Microbiologie Fondamentale et Pathogénicité [MFP] | |
| dc.contributor.author | CARLON-ANDRES, Irene | |
| hal.structure.identifier | Microbiologie Fondamentale et Pathogénicité [MFP] | |
| dc.contributor.author | RAGUES, Jessica | |
| dc.contributor.author | PORT, Sarah | |
| hal.structure.identifier | Microbiologie Fondamentale et Pathogénicité [MFP] | |
| dc.contributor.author | WODRICH, Harald | |
| dc.contributor.author | KEHLENBACH, Ralph H | |
| dc.date.accessioned | 2024-09-30T10:19:24Z | |
| dc.date.available | 2024-09-30T10:19:24Z | |
| dc.date.issued | 2022-02-09 | |
| dc.identifier.issn | 1098-5514 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/202032 | |
| dc.description.abstractEn | After receptor-mediated endocytosis and endosomal escape, adenoviral capsids can travel via microtubule organizing centers to the nuclear envelope. Upon capsid disassembly, viral genome import into nuclei of interphase cells then occurs through nuclear pore complexes, involving the nucleoporins Nup214 and Nup358. Import also requires the activity of the classic nuclear export receptor CRM1, as it is blocked by the selective inhibitor leptomycin B. We have now used artificially enucleated as well as mitotic cells to analyze the role of an intact nucleus in different steps of the viral life cycle. In enucleated U2OS cells, viral capsids traveled to the microtubule organizing center, whereas their removal from this complex was blocked, suggesting that this step required nuclear factors. In mitotic cells, on the other hand, CRM1 promoted capsid disassembly and genome release, suggesting a role of this protein that does not require intact nuclear envelopes or nuclear pore complexes and is distinct from its function as a nuclear export receptor. Similar to enucleation, inhibition of CRM1 by leptomycin B also leads to an arrest of adenoviral capsids at the microtubule organizing center. In a small-scale screen using leptomycin B-resistant versions of CRM1, we identified a mutant, CRM1 W142A P143A, that is compromised with respect to adenoviral capsid disassembly in both interphase and mitotic cells. Strikingly, this mutant is capable of exporting cargo proteins out of the nucleus of living cells or digitonin-permeabilized cells, pointing to a role of the mutated region that is not directly linked to nuclear export. A role of nucleoporins and of soluble transport factors in adenoviral genome import into the nucleus of infected cells in interphase has previously been established. The nuclear export receptor CRM1 promotes genome import, but its precise function is not known. Using enucleated and mitotic cells, we showed that CRM1 does not simply function by exporting a crucial factor out of the nucleus that would then trigger capsid disassembly and genome import. Instead, CRM1 has an export-independent role, a notion that is also supported by a mutant, CRM1 W142A P143A, which is export competent but deficient in viral capsid disassembly, in both interphase and mitotic cells. | |
| dc.language.iso | EN | en_US |
| dc.rights | Attribution 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
| dc.subject.en | Active Transport | |
| dc.subject.en | Cell Nucleus | |
| dc.subject.en | Adenoviridae | |
| dc.subject.en | Adenoviridae Infections | |
| dc.subject.en | Capsid | |
| dc.subject.en | Cell Line | |
| dc.subject.en | Genome | |
| dc.subject.en | Viral | |
| dc.subject.en | Host-Pathogen Interactions | |
| dc.subject.en | Humans | |
| dc.subject.en | Karyopherins | |
| dc.subject.en | Microtubules | |
| dc.subject.en | Models | |
| dc.subject.en | Molecular | |
| dc.subject.en | Mutation | |
| dc.subject.en | Nuclear Envelope | |
| dc.subject.en | Protein Conformation | |
| dc.subject.en | Protein Transport | |
| dc.subject.en | Receptors | |
| dc.subject.en | Cytoplasmic and Nuclear | |
| dc.subject.en | Structure-Activity Relationship | |
| dc.subject.en | Virus Replication | |
| dc.subject.en | Exportin 1 Protein | |
| dc.title.en | CRM1 Promotes Capsid Disassembly and Nuclear Envelope Translocation of Adenovirus Independently of Its Export Function. | |
| dc.title.alternative | J Virol | en_US |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1128/jvi.01273-21 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Microbiologie et Parasitologie | en_US |
| dc.identifier.pubmed | 34757845 | en_US |
| bordeaux.journal | Journal of Virology | en_US |
| bordeaux.page | e0127321 | en_US |
| bordeaux.volume | 96 | en_US |
| bordeaux.hal.laboratories | MFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234 | en_US |
| bordeaux.issue | 3 | en_US |
| bordeaux.institution | CNRS | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.import.source | pubmed | |
| hal.identifier | hal-04714441 | |
| hal.version | 1 | |
| hal.date.transferred | 2024-09-30T10:19:26Z | |
| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | true | |
| workflow.import.source | pubmed | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal%20of%20Virology&rft.date=2022-02-09&rft.volume=96&rft.issue=3&rft.spage=e0127321&rft.epage=e0127321&rft.eissn=1098-5514&rft.issn=1098-5514&rft.au=LAGADEC,%20Floriane&CARLON-ANDRES,%20Irene&RAGUES,%20Jessica&PORT,%20Sarah&WODRICH,%20Harald&rft.genre=article |
