Métadonnées
Afficher la notice complètePartager cette publication !
The retinoic acid receptor (RAR) α-specific agonist Am80 (tamibarotene) and other RAR agonists potently inhibit hepatitis B virus transcription from cccDNA.
Langue
EN
Article de revue
Ce document a été publié dans
Antiviral Research. 2019-08-01, vol. 168, p. 146-155
Résumé en anglais
Chronic infection with the human Hepatitis B virus (HBV) is a major global health problem. Hepatitis D virus (HDV) is a satellite of HBV that uses HBV envelope proteins for cell egress and entry. Using infection systems ...Lire la suite >
Chronic infection with the human Hepatitis B virus (HBV) is a major global health problem. Hepatitis D virus (HDV) is a satellite of HBV that uses HBV envelope proteins for cell egress and entry. Using infection systems encoding the HBV/HDV receptor human sodium taurocholate co-transporting polypeptide (NTCP), we screened 1181 FDA-approved drugs applying markers for interference for HBV and HDV infection. As one primary hit we identified Acitretin, a retinoid, as an inhibitor of HBV replication and HDV release. Based on this, other retinoic acid receptor (RAR) agonists with different specificities were found to interfere with HBV replication, verifying that the retinoic acid receptor pathway regulates replication. Of the eight agonists investigated, RARα-specific agonist Am80 (tamibarotene) was most active. Am80 reduced secretion of HBeAg and HBsAg with ICs 12 days after removal of the drug. HBV genotypes B, D, and E were equally inhibited. By contrast, Am80 did not affect HBV replication in transfected cells or HepG2.2.15 cells, which carry an integrated HBV genome. In conclusion, our results indicate a persistent inhibition of HBV transcription by Am80, which might be used for drug repositioning.< Réduire
Mots clés en anglais
Acitretin
Antiviral Agents
Benzoates
Cells
Cultured
DNA
Circular
DNA
Viral
Hepatitis B Surface Antigens
Hepatitis B e Antigens
Hepatitis B virus
Hepatitis Delta Virus
Hepatocytes
Humans
RNA
Viral
Receptors
Retinoic Acid
Tetrahydronaphthalenes
Transcription
Genetic
Unités de recherche