The antiviral effects of human microRNA miR-302c-3p against hepatitis B virus infection.
Aliment Pharmacol Ther
; 49(8): 1060-1070, 2019 04.
Article
en En
| MEDLINE
| ID: mdl-30828831
ABSTRACT
BACKGROUND:
Conventional treatments of chronic hepatitis B virus (HBV) infection rarely achieve a decline of serum hepatitis B surface antigen (HBsAg) levels and eradication of the virus.AIM:
To elucidate the antiviral mechanisms of a human microRNA, miR-302c-3p, against HBV replication.METHODS:
The antiviral effect of miR-302c-3p was evaluated in vitro and in vivo by transfecting the miR-302c-3p mimic into HBV-infected HepG2-hNTCP-C4 cells and HBV transgenic mice respectively.RESULTS:
miR-302c-3p decreased not only HBV replication but also production of HBsAg. Pregenomic RNA and HBsAg mRNA concentrations decreased in the cells treated with miR-302c-3p. Interestingly, the amount of cccDNA was significantly reduced in the miR-302c-3p-treated cells, in association with disappearance of the HBV core protein. An RNA immunoprecipitation assay showed that miR-302c-3p decreased the binding of the HBV polymerase to the pregenomic RNA by hybridising with the ε-loop region. A number of host genes were downregulated in miR-302c-3p-treated cells, including BMPR2 and HNF4A. Knockdown of these two genes by corresponding siRNAs also suppressed HBV replication and HBsAg secretion. The antiviral effect of miR-302c-3p was also observed in HBV transgenic mice.CONCLUSION:
miR-302c-3p had anti-HBV activity, in vitro and in vivo, via several mechanisms.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Virus de la Hepatitis B
/
Hepatitis B Crónica
/
MicroARNs
Límite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
Aliment Pharmacol Ther
Asunto de la revista:
FARMACOLOGIA
/
GASTROENTEROLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2019
Tipo del documento:
Article
País de afiliación:
Japón