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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Frontiers Media S.A.
2025-02-01
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| 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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| author | Amita Singh Victor Fourcassié Victor Fourcassié Karen Cristine Gonçalves Dos Santos Hocine Chelbi Natacha Merindol Arnaud Droit Arnaud Droit Hugo Germain Lionel Berthoux |
| author_facet | Amita Singh Victor Fourcassié Victor Fourcassié Karen Cristine Gonçalves Dos Santos Hocine Chelbi Natacha Merindol Arnaud Droit Arnaud Droit Hugo Germain Lionel Berthoux |
| author_sort | Amita Singh |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9891d38f022c41069bdb8f1e6a84ec34 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Virology |
| spelling | doaj-art-9891d38f022c41069bdb8f1e6a84ec342025-02-03T06:33:42ZengFrontiers Media S.A.Frontiers in Virology2673-818X2025-02-01510.3389/fviro.2025.15471761547176Effects of GS-CA1 on nuclear envelope-associated early HIV-1 infection stepsAmita Singh0Victor Fourcassié1Victor Fourcassié2Karen Cristine Gonçalves Dos Santos3Hocine Chelbi4Natacha Merindol5Arnaud Droit6Arnaud Droit7Hugo Germain8Lionel Berthoux9Department of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC, CanadaProteomics Platform of the Centre Hospitalier Universitaire de Québec - Université Laval, Québec, QC, CanadaCentre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval, Québec, QC, CanadaDepartment of Chemistry, Biochemistry and Physics, Université du Québec à Trois-Rivières, Trois-Rivières, QC, CanadaDepartment of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC, CanadaCentre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval, Québec, QC, CanadaProteomics Platform of the Centre Hospitalier Universitaire de Québec - Université Laval, Québec, QC, CanadaCentre de recherche du Centre Hospitalier Universitaire de Québec - Université Laval, Québec, QC, CanadaDepartment of Chemistry, Biochemistry and Physics, Université du Québec à Trois-Rivières, Trois-Rivières, QC, CanadaDepartment of Medical Biology, Université du Québec à Trois-Rivières, Trois-Rivières, QC, CanadaThe 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.https://www.frontiersin.org/articles/10.3389/fviro.2025.1547176/fullHIV-1HIV-1 capsidGS-CA1mass spectrometrynuclear pore complexnuclear envelope |
| spellingShingle | Amita Singh Victor Fourcassié Victor Fourcassié Karen Cristine Gonçalves Dos Santos Hocine Chelbi Natacha Merindol Arnaud Droit Arnaud Droit Hugo Germain Lionel Berthoux Effects of GS-CA1 on nuclear envelope-associated early HIV-1 infection steps Frontiers in Virology HIV-1 HIV-1 capsid GS-CA1 mass spectrometry nuclear pore complex nuclear envelope |
| title | Effects of GS-CA1 on nuclear envelope-associated early HIV-1 infection steps |
| title_full | Effects of GS-CA1 on nuclear envelope-associated early HIV-1 infection steps |
| title_fullStr | Effects of GS-CA1 on nuclear envelope-associated early HIV-1 infection steps |
| title_full_unstemmed | Effects of GS-CA1 on nuclear envelope-associated early HIV-1 infection steps |
| title_short | Effects of GS-CA1 on nuclear envelope-associated early HIV-1 infection steps |
| title_sort | effects of gs ca1 on nuclear envelope associated early hiv 1 infection steps |
| topic | HIV-1 HIV-1 capsid GS-CA1 mass spectrometry nuclear pore complex nuclear envelope |
| url | https://www.frontiersin.org/articles/10.3389/fviro.2025.1547176/full |
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