In vivo HIV-1 nuclear condensates safeguard against cGAS and license reverse transcription - Institut Pasteur
Article Dans Une Revue EMBO Journal Année : 2024

In vivo HIV-1 nuclear condensates safeguard against cGAS and license reverse transcription

James Di Santo

Résumé

Entry of viral capsids into the nucleus induces the formation of biomolecular condensates called HIV-1 membraneless organelles (HIV-1-MLOs). Several questions remain about their persistence, in vivo formation, composition, and function. Our study reveals that HIV-1-MLOs persisted for several weeks in infected cells, and their abundance correlated with viral infectivity. Using an appropriate animal model, we show that HIV-1-MLOs were formed in vivo during acute infection. To explore the viral structures present within these biomolecular condensates, we used a combination of double immunogold labeling, electron microscopy and tomography, and unveiled a diverse array of viral core structures. Our functional analyses showed that HIV-1-MLOs remained stable during treatment with a reverse transcriptase inhibitor, maintaining the virus in a dormant state. Drug withdrawal restored reverse transcription, promoting efficient virus replication akin to that observed in latently infected patients on antiretroviral therapy. However, when HIV-1 MLOs were deliberately disassembled by pharmacological treatment, we observed a complete loss of viral infectivity. Our findings show that HIV-1 MLOs shield the final reverse transcription product from host immune detection.
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In vivo HIV-1 nuclear condensates safeguard against cGAS and license reverse transcription - ay-et-al-2024-in-vivo-hiv-1-nuclear-condensates-safeguard-against-cgas-and-license-reverse-transcription.pdf (16.13 Mo) Télécharger le fichier
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pasteur-04826770 , version 1 (09-12-2024)

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Selen Ay, Julien Burlaud-Gaillard, Anastasia Gazi, Yevgeniy Tatirovsky, Céline Cuche, et al.. In vivo HIV-1 nuclear condensates safeguard against cGAS and license reverse transcription. EMBO Journal, 2024, ⟨10.1038/s44318-024-00316-w⟩. ⟨pasteur-04826770⟩
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