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BRIEF RESEARCH REPORT article

Front. Virol.
Sec. Antivirals and Vaccines
Volume 5 - 2025 | doi: 10.3389/fviro.2025.1547176

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

Provisionally accepted
Amita Singh Amita Singh 1Victor Fourcassié Victor Fourcassié 2Karen Cristine Gonçalves Dos Santos Karen Cristine Gonçalves Dos Santos 1Hocine Chelbi Hocine Chelbi 1Natacha Merindol Natacha Merindol 1Arnaud Droit Arnaud Droit 2Hugo Germain Hugo Germain 1Lionel Berthoux Lionel Berthoux 1*
  • 1 Université du Québec à Trois-Rivières, Trois-Rivières, Canada
  • 2 Centre de Recherche du CHU de Québec, Québec City, Quebec, Canada

The final, formatted version of the article will be published soon.

    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 IFNβ. 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.

    Keywords: HIV-1, HIV-1 capsid, GS-CA1, Mass Spectrometry, nuclear pore complex, nuclear

    Received: 17 Dec 2024; Accepted: 15 Jan 2025.

    Copyright: © 2025 Singh, Fourcassié, Gonçalves Dos Santos, Chelbi, Merindol, Droit, Germain and Berthoux. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Lionel Berthoux, Université du Québec à Trois-Rivières, Trois-Rivières, Canada

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.