Effects of GS-CA1 on nuclear envelope-associated early HIV-1 infection steps

Singh, A., Fourcassié, V., dos Santos, K. C. G., Chelbi, H., Merindol, N., Droit, A., Germain, H. et Berthoux, L. (2025). Effects of GS-CA1 on nuclear envelope-associated early HIV-1 infection steps. Frontiers in Virology, 5 . Article 1547176. ISSN 2673-818X DOI 10.3389/fviro.2025.1547176

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Résumé

Abstract

The novel HIV-1 drugs GS-CA1 and the recently approved lenacapavir (GS-6207) target the viral structural protein capsid (CA). However, their multiple mechanisms of action have not been fully characterized. Here, we investigated the effects of GS-CA1 on the early stages of HIV-1 infection, specifically the steps involving the nuclear envelope, in comparison to the antiviral cytokine IFN-β. Mass spectrometry data indicated that nuclear envelope proteins were only modestly affected by either GS-CA1 treatment or HIV-1 infection, but combining the two had a more significant impact, altering the levels of many proteins including proteasomal components. GS-CA1 induced a small but clear accumulation of HIV-1 capsid cores at nuclear pores, as seen by microscopy, whereas IFN-β caused a strong accumulation of HIV-1 cores at the nuclear envelope but not specifically at nuclear pores. These observations are consistent with GS-CA1 inhibiting the nuclear translocation of HIV-1 capsid cores through nuclear pores.

Type de document:	Article
Mots-clés libres:	Mass spectrometry HIV-1 Interferon Nuclear pore complex HIV-1 capsid GS-CA1 Nuclear envelope
Date de dépôt:	25 mars 2025 17:38
Dernière modification:	25 mars 2025 17:38
Version du document déposé:	Version officielle de l'éditeur
URI:	https://depot-e.uqtr.ca/id/eprint/11772

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