HIV-induced membraneless organelles orchestrate post-nuclear entry steps  

作　　者：Viviana Scoca Renaud Morin Maxence Collard Jean-Yves Tinevez Francesca Di Nunzio 

机构地区：[1]Advanced Molecular Virology Unit,Department of Virology,Institut Pasteur,UniversitéParis Cité,75015 Paris,France [2]Imactiv-3D,1 Place Pierre Potier,31106 Toulouse,France [3]Image Analysis Hub/C2RT,Institut Pasteur,UniversitéParis Cité,75015 Paris,France

出　　处：《Journal of Molecular Cell Biology》2022年第11期9-23,共15页分子细胞生物学报（英文版）

基　　金：funded by the ANRS REACTing grant(ECTZ88162)with a nominative PhD student fellowship(ECTZ88177)for V.S.;the Sidaction/Fondation pour la Recherche Médicale(FRM)grant(VIH20170718001);Institut Pasteur.

摘　　要：HIV integration occurs in chromatin sites that favor the release of high levels of viral progeny;alternatively, the virus is alsoable to discreetly coexist with the host. The viral infection perturbs the cellular environment inducing the remodelling of thenuclear landscape. Indeed, HIV-1 triggers the nuclear clustering of the host factor CPSF6, but the underlying mechanism ispoorly understood. Our data indicate that HIV usurps a recently discovered biological phenomenon, called liquid–liquid phaseseparation, to hijack the host cell. We observed CPSF6 clusters as part of HIV-induced membraneless organelles (HIV-1 MLOs) inmacrophages, one of the main HIV target cell types. We describe that HIV-1 MLOs follow phase-separation rules and representfunctional biomolecular condensates. We highlight HIV-1 MLOs as hubs of nuclear reverse transcription, while the double-strandedviral DNA, once formed, rapidly migrates outside these structures. Transcription-competent proviruses localize outside but nearHIV-1 MLOs in LEDGF-abundant regions, known to be active chromatin sites. Therefore, HIV-1 MLOs orchestrate viral events priorto the integration step and create a favorable environment for the viral replication. This study uncovers single functional host–viralcomplexes in their nuclear landscape, which is markedly restructured by HIV-1.

关 键 词：HIV nuclear condensates nuclear remodelling phase separation reverse transcription 

分 类 号：R512.91[医药卫生—内科学]