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TitleIn vivo HIV-1 nuclear condensates safeguard against cGAS and license reverse transcription.
Journal, issue, pagesEMBO J, Vol. 44, Issue 1, Page 166-199, Year 2025
Publish dateDec 2, 2024
AuthorsSelen Ay / Julien Burlaud-Gaillard / Anastasia Gazi / Yevgeniy Tatirovsky / Celine Cuche / Jean-Sebastien Diana / Viviana Scoca / James P Di Santo / Philippe Roingeard / Fabrizio Mammano / Francesca Di Nunzio /
PubMed AbstractEntry 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 ...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.
External linksEMBO J / PubMed:39623137 / PubMed Central
MethodsEM (tomography)
Structure data

EMDB-51462: Nuclear HIV-1 Condensate
Method: EM (tomography)

EMDB-51466: HIV-1 Nuclear Condensate under NEV treatment
Method: EM (tomography)

Source
  • HIV-1 vector pNL4-3 (others)

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