R88-APOBEC3Gm Inhibits the Replication of Both Drug-resistant Strains of HIV-1 and Viruses Produced From Latently Infected Cells
Notice bibliographique
Résumé
Human immunodeficiency virus type 1 (HIV-1) drug resistance and the latent reservoir are the two major obstacles to effectively controlling and curing HIV-1 infection. Therefore, it is critical to develop therapeutic strategies specifically targeting these two obstacles. Recently, we described a novel anti-HIV approach based on a modified human intrinsic restriction factor, R88-APOBEC3G (R88-A3G). In this study, we further characterized the antiviral potential of R88-A3GD128K (R88-A3Gm) against drug-resistant strains of HIV-1 and viruses produced from latently infected cells. We delivered R88-A3Gm into target cells using a doxycycline (Dox)-inducible lentiviral vector and demonstrated that its expression and antiviral activity were highly regulated by Dox. In the presence of Dox, R88-A3Gm–transduced T cells were resistant to infection caused by wild-type and various drug-resistant strains of HIV-1. Moreover, when the R88-A3Gm–expressing vector was transduced into the HIV-1 latently infected ACH-2 cell line or human CD4+ T cells, on activation by phorbol-12-myristate-13-acetate or phytohemaglutinin, R88-A3Gm was able to curtail the replication of progeny viruses. Altogether, these data clearly indicate that R88-A3Gm is a highly potent HIV-1 inhibitor, and R88-A3Gm–based anti-HIV gene therapy is capable of targeting both active and latent HIV-1–infected cells to prevent subsequent viral replication and dissemination. Human immunodeficiency virus type 1 (HIV-1) drug resistance and the latent reservoir are the two major obstacles to effectively controlling and curing HIV-1 infection. Therefore, it is critical to develop therapeutic strategies specifically targeting these two obstacles. Recently, we described a novel anti-HIV approach based on a modified human intrinsic restriction factor, R88-APOBEC3G (R88-A3G). In this study, we further characterized the antiviral potential of R88-A3GD128K (R88-A3Gm) against drug-resistant strains of HIV-1 and viruses produced from latently infected cells. We delivered R88-A3Gm into target cells using a doxycycline (Dox)-inducible lentiviral vector and demonstrated that its expression and antiviral activity were highly regulated by Dox. In the presence of Dox, R88-A3Gm–transduced T cells were resistant to infection caused by wild-type and various drug-resistant strains of HIV-1. Moreover, when the R88-A3Gm–expressing vector was transduced into the HIV-1 latently infected ACH-2 cell line or human CD4+ T cells, on activation by phorbol-12-myristate-13-acetate or phytohemaglutinin, R88-A3Gm was able to curtail the replication of progeny viruses. Altogether, these data clearly indicate that R88-A3Gm is a highly potent HIV-1 inhibitor, and R88-A3Gm–based anti-HIV gene therapy is capable of targeting both active and latent HIV-1–infected cells to prevent subsequent viral replication and dissemination.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».