Establishment of a hepatitis B virus reporter system harboring a HiBiT-tag in the PreS2 region.
J Infect Dis
; 2024 Jul 11.
Article
en En
| MEDLINE
| ID: mdl-38990781
ABSTRACT
BACKGROUND:
Approximately 296 million people suffer from chronic hepatitis B (CHB) caused by hepatitis B virus (HBV). Current standard treatment, nucleos(t)ide analogs, are not efficient enough to eradicate HBV from the hepatocytes. Thus, developing new drugs for CHB is desired to achieve complete cure.METHODS:
Here we established a novel HBV reporter system, HBV-HiBiT-PS2, to screen new drugs for CHB. HBV-HiBiT-PS2 was constructed by introducing a HiBiT-tag at the 5'-end of PreS2 and introduced into HepG2-NTCP cells. Culture supernatant containing HBV-HiBiT-PS2 virions was fractionated by a sucrose density gradient ultracentrifugation to characterize their components. Replication kinetics and reporter function of HBV-HiBiT-PS2 were determined by analyzing the parameters for HBV replication in the presence or absence of HBV inhibitors.RESULTS:
HBV-HiBiT-PS2 could be used for monitoring most of the replication cycle of HBV. The effects of well-characterized HBV inhibitors could be evaluated by the HiBiT activity. HBV-HiBiT-PS2 could be specialized for screening secretion inhibitors for hepatitis B surface antigen (HBsAg) because most of the HiBiT activity was derived from subviral particles which are the multimers of HBsAg.CONCLUSIONS:
We demonstrated that HBV-HiBiT-PS2 would be a robust tool for screening novel drugs, especially HBsAg secretion inhibitors, targeted for CHB.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
J Infect Dis
Año:
2024
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Estados Unidos