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

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, specifical...

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Bibliographic Details
Main Authors: Amita Singh, Victor Fourcassié, Karen Cristine Gonçalves Dos Santos, Hocine Chelbi, Natacha Merindol, Arnaud Droit, Hugo Germain, Lionel Berthoux
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Virology
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Online Access:https://www.frontiersin.org/articles/10.3389/fviro.2025.1547176/full
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Summary: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.
ISSN:2673-818X