RT Journal Article
SR Electronic
T1 HIV-induced membraneless organelles orchestrate post-nuclear entry steps
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.11.17.385567
DO 10.1101/2020.11.17.385567
A1 Viviana Scoca
A1 Renaud Morin
A1 Maxence Collard
A1 Jean-Yves Tinevez
A1 Francesca Di Nunzio
YR 2022
UL http://biorxiv.org/content/early/2022/09/30/2020.11.17.385567.abstract
AB HIV integration occurs in chromatin sites that favor the release of high levels of viral progeny, alternatively the virus is also able to discreetly coexist with the host. The viral infection perturbs the cellular environment inducing the remodeling of the nuclear landscape. Indeed, HIV-1 triggers the nuclear clustering of the host factor CPSF6, but the underlying mechanism is poorly understood. Our data indicate that HIV usurps a recently discovered biological phenomenon, called liquid-liquid phase separation (LLPS), to hijack the host cell. We observed CPSF6 clusters as part of HIV-induced membraneless organelles (HIV-1 MLOs) in macrophages, which are one of the main HIV target cells. We describe that HIV-1 MLOs follow phase separation rules and represent functional biomolecular condensates. We highlight HIV-1 MLOs as hubs of nuclear reverse transcription, while the double stranded viral DNA, once formed, rapidly migrates outside these structures. Transcription-competent proviruses localize outside, but near HIV-1 MLOs, in LEDGF-abundant regions, known to be active chromatin sites. Therefore, HIV-1 MLOs orchestrate viral events prior to the integration step and create a favorable environment for the viral replication. This study uncovers single functional host-viral complexes in their nuclear landscape, which is markedly restructured by HIV-1.Competing Interest StatementThe authors have declared no competing interest.