HIV-Induced CPSF6 Condensates

Selen, A; Nunzio, Francesca Di

doi:10.1016/j.jmb.2023.168094

Cited by 14 publications

(3 citation statements)

References 123 publications

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“…Furthermore, shortly after the PIC enters the nucleus, condensates of CPSF6 form around clusters of RTCs/PICs ( Rensen et al., 2021 ; Scoca et al., 2022 ). These CPSF6 membraneless organelles have been proposed to be niches where RTCs/PICs mature just before integration ( Ay and Di Nunzio, 2023 ).…”

Section: The Intermediate To Late Events Post-fusionmentioning

confidence: 99%

The capsid revolution

Taylor,

Fassati

2023

Journal of Molecular Cell Biology

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Lenacapavir, targeting the HIV-1 capsid, is the first-in-class antiretroviral drug recently approved for clinical use. The development of Lenacapavir is attributed to the remarkable progress in our understanding of the capsid protein made during the last few years. Considered little more than a component of the virus shell to be shed early during infection, capsid has been found to be a key player in the HIV-1 life cycle by interacting with multiple host cell factors, entering the nucleus, and directing integration. Here, we describe the key advances that led to this “capsid revolution”.

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Section: The Intermediate To Late Events Post-fusionmentioning

confidence: 99%

The capsid revolution

Taylor,

Fassati

2023

Journal of Molecular Cell Biology

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“…CPSF6 is a nuclear protein involved in alternative polyadenylation of pre-mRNA. Together with CPSF5 (also called CFIm25), it forms the heterotetrameric cleavage factor I mammalian (CFIm) complex [27][28][29]. CPSF5 can also form heterotetramers with CPSF7 independently of CPSF6, but the functional differences of the two versions of CFIm are unknown.…”

Section: Introductionmentioning

confidence: 99%

“…CPSF5 can also form heterotetramers with CPSF7 independently of CPSF6, but the functional differences of the two versions of CFIm are unknown. CPSF5 binds RNA and assembles the CFIm complex within a larger Cleavage and Polyadenylation (CPA) complex [27][28][29]. Following HIV-1 infection, CPSF6 relocates from diffuse nuclear staining to discrete puncta that colocalise with SC35-positive nuclear speckles [12,14,18,[30][31][32].…”

Section: Introductionmentioning

confidence: 99%

HIV-1 Capsid Rapidly Induces Long-Lived CPSF6 Puncta in Non-Dividing Cells, but Similar Puncta Already Exist in Uninfected T-Cells

Guedán,

Burley,

Caroe

et al. 2024

Viruses

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The HIV-1 capsid (CA) protein forms the outer shell of the viral core that is released into the cytoplasm upon infection. CA binds various cellular proteins, including CPSF6, that direct HIV-1 integration into speckle-associated domains in host chromatin. Upon HIV-1 infection, CPSF6 forms puncta in the nucleus. Here, we characterised these CPSF6 puncta further in HeLa cells, T-cells and macrophages and confirmed that integration and reverse transcription are not required for puncta formation. Indeed, we found that puncta formed very rapidly after infection, correlating with the time that CA entered the nucleus. In aphidicolin-treated HeLa cells and macrophages, puncta were detected for the length of the experiment, suggesting that puncta are only lost upon cell division. CA still co-localised with CPSF6 puncta at the latest time points, considerably after the peak of reverse transcription and integration. Intriguingly, the number of puncta induced in macrophages did not correlate with the MOI or the total number of nuclear speckles present in each cell, suggesting that CA/CPSF6 is only directed to a few nuclear speckles. Furthermore, we found that CPSF6 already co-localised with nuclear speckles in uninfected T-cells, suggesting that HIV-1 promotes a natural behaviour of CPSF6.

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Characterization of Nuclear HIV-Induced Membraneless Organelles Through Fluorescence Microscopy

Scoca,

Di Nunzio

2024

Methods in Molecular Biology

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HIV-Induced CPSF6 Condensates

Cited by 14 publications

References 123 publications

The capsid revolution

The capsid revolution

HIV-1 Capsid Rapidly Induces Long-Lived CPSF6 Puncta in Non-Dividing Cells, but Similar Puncta Already Exist in Uninfected T-Cells

Characterization of Nuclear HIV-Induced Membraneless Organelles Through Fluorescence Microscopy

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