Academic Journal
Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein
| العنوان: | Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein |
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| المؤلفون: | Nangola, Sawitree, Urvoas, Agathe, Valerio-Lepiniec, Marie, Khamaikawin, Wannisa, Sakkhachornphop, Supacha, Hong, Saw-See, Boulanger, Pierre, Minard, Philippe, Tayapiwatana, Chatchai |
| المساهمون: | Chiang Mai University (CMU), Université Paris-Sud - Paris 11 (UP11), Rétrovirus et Pathologie Comparée, Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Université de Lyon (COMUE) |
| المصدر: | ISSN: 1742-4690 ; Retrovirology ; https://hal.inrae.fr/hal-02642663 ; Retrovirology, 2012, 9, 27 p. ⟨10.1186/1742-4690-9-17⟩. |
| بيانات النشر: | HAL CCSD BioMed Central |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | hiv-1, hiv-1 assembly, gag polyprotein, virus assembly inhibitor, ankyrins, artificial ankyrin library, amino acid sequence, ca domain, intracellular antiviral agent, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology |
| الوصف: | International audience ; BACKGROUND: Ankyrins are cellular mediators of a number of essential protein-protein interactions. Unlike intrabodies, ankyrins are composed of highly structured repeat modules characterized by disulfide bridge-independent folding. Artificial ankyrin molecules, designed to target viral components, might act as intracellular antiviral agents and contribute to the cellular immunity against viral pathogens such as HIV-1. RESULTS: A phage-displayed library of artificial ankyrins was constructed, and screened on a polyprotein made of the fused matrix and capsid domains (MA-CA) of the HIV-1 Gag precursor. An ankyrin with three modules named Ank(GAG)1D4 (16.5 kDa) was isolated. Ank(GAG)1D4 and MA-CA formed a protein complex with a stoichiometry of 1:1 and a dissociation constant of K(d) ~ 1 muM, and the Ank(GAG)1D4 binding site was mapped to the N-terminal domain of the CA, within residues 1-110. HIV-1 production in SupT1 cells stably expressing Ank(GAG)1D4 in both N-myristoylated and non-N-myristoylated versions was significantly reduced compared to control cells. Ank(GAG)1D4 expression also reduced the production of MLV, a phylogenetically distant retrovirus. The Ank(GAG)1D4-mediated antiviral effect on HIV-1 was found to occur at post-integration steps, but did not involve the Gag precursor processing or cellular trafficking. Our data suggested that the lower HIV-1 progeny yields resulted from the negative interference of Ank(GAG)1D4-CA with the Gag assembly and budding pathway. CONCLUSIONS: The resistance of Ank(GAG)1D4-expressing cells to HIV-1 suggested that the CA-targeted ankyrin Ank(GAG)1D4 could serve as a protein platform for the design of a novel class of intracellular inhibitors of HIV-1 assembly based on ankyrin-repeat modules. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/22348230; hal-02642663; https://hal.inrae.fr/hal-02642663; https://hal.inrae.fr/hal-02642663/document; https://hal.inrae.fr/hal-02642663/file/2012_Nangola_Retrovirology_1.pdf; PRODINRA: 168036; PUBMED: 22348230; WOS: 000301721900001 |
| DOI: | 10.1186/1742-4690-9-17 |
| الاتاحة: | https://hal.inrae.fr/hal-02642663 https://hal.inrae.fr/hal-02642663/document https://hal.inrae.fr/hal-02642663/file/2012_Nangola_Retrovirology_1.pdf https://doi.org/10.1186/1742-4690-9-17 |
| Rights: | http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.7C86AA73 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/1742-4690-9-17 |
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