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 envi...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.展开更多
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.
文摘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.
