ALT, alanine aminotransferase
Antivirals
Bulevirtide
CIs, capsid inhibitors
Capsid inhibitors
Core protein
Covalently closed circular DNA
DHBV, duck hepatitis B virus
HBV DNA integration
HBV persistence
HBV, hepatitis B virus
HBcAg
HBsAg, hepatitis B virus surface antigen
Hepcludex
Myrcludex B
NC, naked capsids
NTCP, sodium taurocholate cotransporting polypeptide
NUCs, nucleos(t)ide analogues
ORF, open reading frame
PEG, polyethylene glycol
PHH, primary human hepatocytes
SN, supernatant
VP, virions
WT, wild-type
cccDNA, covalently closed circular DNA
dpi, days post inoculation
mge, multiplicity of genomic equivalent
pgRNA, pregenomic RNA
rcDNA, relaxed circular DNA
vge, viral genome equivalents
Journal
JHEP reports : innovation in hepatology
ISSN: 2589-5559
Titre abrégé: JHEP Rep
Pays: Netherlands
ID NLM: 101761237
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
21
07
2020
revised:
24
08
2020
accepted:
20
09
2020
entrez:
1
1
2021
pubmed:
2
1
2021
medline:
2
1
2021
Statut:
epublish
Résumé
Chronic HBV infection cannot be cured by current therapeutics owing to their limited ability to reduce covalently closed circular (ccc)DNA levels in the livers of infected individuals. Therefore, greater understanding of the molecular determinants of cccDNA formation and persistence is required. One key issue is the extent to which We engineered an infectious HBV mutant with a genome encoding a stop codon at position T67 in the HBV core open reading frame (ΔHBc HBV). Importantly, ΔHBc HBV virions cannot initiate nucleocapsid synthesis upon infection. Long-term ΔHBc and wild-type (WT) HBV resulted in comparable expression of HBV surface antigen (HBsAg), which could be blocked using the entry inhibitor Myrcludex B, confirming Our results imply that The hepatitis B virus can maintain itself in the liver for a patient's lifetime, causing liver injury and cancer. We have clarified exactly how it maintains itself in an infected cell. This now means we have a better idea at how to target the virus and cure a chronic infection.
Sections du résumé
BACKGROUND & AIMS
OBJECTIVE
Chronic HBV infection cannot be cured by current therapeutics owing to their limited ability to reduce covalently closed circular (ccc)DNA levels in the livers of infected individuals. Therefore, greater understanding of the molecular determinants of cccDNA formation and persistence is required. One key issue is the extent to which
METHODS
METHODS
We engineered an infectious HBV mutant with a genome encoding a stop codon at position T67 in the HBV core open reading frame (ΔHBc HBV). Importantly, ΔHBc HBV virions cannot initiate nucleocapsid synthesis upon infection. Long-term
RESULTS
RESULTS
ΔHBc and wild-type (WT) HBV resulted in comparable expression of HBV surface antigen (HBsAg), which could be blocked using the entry inhibitor Myrcludex B, confirming
CONCLUSIONS
CONCLUSIONS
Our results imply that
LAY SUMMARY
BACKGROUND
The hepatitis B virus can maintain itself in the liver for a patient's lifetime, causing liver injury and cancer. We have clarified exactly how it maintains itself in an infected cell. This now means we have a better idea at how to target the virus and cure a chronic infection.
Identifiants
pubmed: 33385130
doi: 10.1016/j.jhepr.2020.100195
pii: S2589-5559(20)30129-4
pmc: PMC7771110
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100195Informations de copyright
© 2020 The Authors.
Déclaration de conflit d'intérêts
S.U. is co-applicant and co-inventor on patents protecting HBV preS-derived lipopeptides (Myrcludex B) for the use of HBV/HDV entry inhibitors. The other authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.
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