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Modulation of the functional interfaces between retroviral intasomes and the human nucleosome

dc.rights.licenseopenen_US
dc.contributor.authorMAURO, E.
dc.contributor.authorLAPAILLERIE, D.
dc.contributor.authorTUMIOTTO, C.
dc.contributor.authorCHARLIER, C.
dc.contributor.authorMARTINS, F.
dc.contributor.authorSOUSA, S
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorMÉTIFIOT, M.
dc.contributor.authorWEIGEL, P
dc.contributor.authorYAMATSUGU, K.
dc.contributor.authorKANAI, M.
dc.contributor.authorMUNIER-LEHMANN, H.
dc.contributor.authorRICHETTA, C.
dc.contributor.authorBATISSE, J.
dc.contributor.authorRUFF, M.
dc.contributor.authorDELELIS, O.
dc.contributor.authorLESBATS, P.
dc.contributor.authorPARISSI, V.
dc.date.accessioned2023-05-17T08:13:44Z
dc.date.available2023-05-17T08:13:44Z
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182186
dc.description.abstractEnRetroviral integration into cell chromatin requires the formation of integrase-viral DNA complexes, called intasomes, and their interaction with the target DNA wrapped around nucleosomes. To further study this mechanism we developed an alphaLISA approach using the prototype foamy virus (PFV) intasome and human nucleosome. This system allowed us to monitor the association between both partners and investigate the protein/protein and protein/DNA interactions engaged in the association with chromatin. Using this approach, we next screened the chemical OncoSET library and selected small molecules that could modulate the intasome/nucleosome complex. Molecules were selected as acting either on the DNA topology within the nucleosome or on the integrase/histone tail interactions. Within these compounds, doxorubicin and histone binders calixarenes were characterized using biochemical, structural and cellular approaches. These drugs were shown to inhibit PFV and HIV-1 integration in vitro as well as HIV-1 infection in primary PBMCs cells. Our work provides new information about intasome-nucleosome interaction determinants and paves the way for further unedited antiviral strategies that target the final step of intasome/chromatin anchoring.
dc.language.isoENen_US
dc.title.enModulation of the functional interfaces between retroviral intasomes and the human nucleosome
dc.typeDocument de travail - Pré-publicationen_US
dc.identifier.doi10.1101/2022.09.29.510092en_US
dc.subject.halSciences du Vivant [q-bio]/Microbiologie et Parasitologie/Virologieen_US
bordeaux.hal.laboratoriesMFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234en_US
bordeaux.institutionCNRSen_US
bordeaux.import.sourcehal
hal.identifierhal-03819552
hal.version1
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
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