Specific Interaction of DARPin with HIV-1 CA<sub>NTD</sub> Disturbs the Distribution of Gag, RNA Packaging, and Tetraspanin Remodelling in the Membrane
A designed repeat scaffold protein (Ank<sup>GAG</sup>1D4) recognizing the human immunodeficiency virus-1 (HIV-1) capsid (CA) was formerly established with antiviral assembly. Here, we investigated the molecular mechanism of Ank<sup>GAG</sup>1D4 function during the late stages...
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| Format: | Article |
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MDPI AG
2022-04-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/4/824 |
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| author | Sutpirat Moonmuang Rawiwan Maniratanachote Paninee Chetprayoon Kanokporn Sornsuwan Weeraya Thongkum Koollawat Chupradit Chatchai Tayapiwatana |
| author_facet | Sutpirat Moonmuang Rawiwan Maniratanachote Paninee Chetprayoon Kanokporn Sornsuwan Weeraya Thongkum Koollawat Chupradit Chatchai Tayapiwatana |
| author_sort | Sutpirat Moonmuang |
| collection | DOAJ |
| description | A designed repeat scaffold protein (Ank<sup>GAG</sup>1D4) recognizing the human immunodeficiency virus-1 (HIV-1) capsid (CA) was formerly established with antiviral assembly. Here, we investigated the molecular mechanism of Ank<sup>GAG</sup>1D4 function during the late stages of the HIV-1 replication cycle. By applying stimulated emission-depletion (STED) microscopy, Gag polymerisation was interrupted at the plasma membrane. Disturbance of Gag polymerisation triggered Gag accumulation inside producer cells and trapping of the CD81 tetraspanin on the plasma membrane. Moreover, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) experiments were performed to validate the packaging efficiency of RNAs. Our results advocated that Ank<sup>GAG</sup>1D4 interfered with the Gag precursor protein from selecting HIV-1 and cellular RNAs for encapsidation into viral particles. These findings convey additional information on the antiviral activity of Ank<sup>GAG</sup>1D4 at late stages of the HIV-1 life cycle, which is potential for an alternative anti-HIV molecule. |
| first_indexed | 2024-03-09T04:06:53Z |
| format | Article |
| id | doaj.art-b7ee4f3850714b16a46253518024b847 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T04:06:53Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-b7ee4f3850714b16a46253518024b8472023-12-03T14:04:42ZengMDPI AGViruses1999-49152022-04-0114482410.3390/v14040824Specific Interaction of DARPin with HIV-1 CA<sub>NTD</sub> Disturbs the Distribution of Gag, RNA Packaging, and Tetraspanin Remodelling in the MembraneSutpirat Moonmuang0Rawiwan Maniratanachote1Paninee Chetprayoon2Kanokporn Sornsuwan3Weeraya Thongkum4Koollawat Chupradit5Chatchai Tayapiwatana6Center of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandToxicology and Bio Evaluation Service Center (TBES), National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, ThailandToxicology and Bio Evaluation Service Center (TBES), National Science and Technology Development Agency (NSTDA), Pathum Thani 12120, ThailandCenter of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandCenter of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandCenter of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandCenter of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, ThailandA designed repeat scaffold protein (Ank<sup>GAG</sup>1D4) recognizing the human immunodeficiency virus-1 (HIV-1) capsid (CA) was formerly established with antiviral assembly. Here, we investigated the molecular mechanism of Ank<sup>GAG</sup>1D4 function during the late stages of the HIV-1 replication cycle. By applying stimulated emission-depletion (STED) microscopy, Gag polymerisation was interrupted at the plasma membrane. Disturbance of Gag polymerisation triggered Gag accumulation inside producer cells and trapping of the CD81 tetraspanin on the plasma membrane. Moreover, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) experiments were performed to validate the packaging efficiency of RNAs. Our results advocated that Ank<sup>GAG</sup>1D4 interfered with the Gag precursor protein from selecting HIV-1 and cellular RNAs for encapsidation into viral particles. These findings convey additional information on the antiviral activity of Ank<sup>GAG</sup>1D4 at late stages of the HIV-1 life cycle, which is potential for an alternative anti-HIV molecule.https://www.mdpi.com/1999-4915/14/4/824HIV-1Gag polyproteinvirus assembly inhibitorankyrintetraspanin |
| spellingShingle | Sutpirat Moonmuang Rawiwan Maniratanachote Paninee Chetprayoon Kanokporn Sornsuwan Weeraya Thongkum Koollawat Chupradit Chatchai Tayapiwatana Specific Interaction of DARPin with HIV-1 CA<sub>NTD</sub> Disturbs the Distribution of Gag, RNA Packaging, and Tetraspanin Remodelling in the Membrane Viruses HIV-1 Gag polyprotein virus assembly inhibitor ankyrin tetraspanin |
| title | Specific Interaction of DARPin with HIV-1 CA<sub>NTD</sub> Disturbs the Distribution of Gag, RNA Packaging, and Tetraspanin Remodelling in the Membrane |
| title_full | Specific Interaction of DARPin with HIV-1 CA<sub>NTD</sub> Disturbs the Distribution of Gag, RNA Packaging, and Tetraspanin Remodelling in the Membrane |
| title_fullStr | Specific Interaction of DARPin with HIV-1 CA<sub>NTD</sub> Disturbs the Distribution of Gag, RNA Packaging, and Tetraspanin Remodelling in the Membrane |
| title_full_unstemmed | Specific Interaction of DARPin with HIV-1 CA<sub>NTD</sub> Disturbs the Distribution of Gag, RNA Packaging, and Tetraspanin Remodelling in the Membrane |
| title_short | Specific Interaction of DARPin with HIV-1 CA<sub>NTD</sub> Disturbs the Distribution of Gag, RNA Packaging, and Tetraspanin Remodelling in the Membrane |
| title_sort | specific interaction of darpin with hiv 1 ca sub ntd sub disturbs the distribution of gag rna packaging and tetraspanin remodelling in the membrane |
| topic | HIV-1 Gag polyprotein virus assembly inhibitor ankyrin tetraspanin |
| url | https://www.mdpi.com/1999-4915/14/4/824 |
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