Front Cell Infect Microbiol. 2020 Apr 16;10:158. doi: 10.3389/fcimb.2020.00158. eCollection 2020.
Difluoromethylornithine, a Decarboxylase 1 Inhibitor, Suppresses Hepatitis B Virus Replication by Reducing HBc Protein Levels.
Mao B1, Wang Z1, Pi S1, Long Q1, Chen K1, Cui J1, Huang A1, Hu Y1.
Author information
1
Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Abstract
Current treatments of hepatitis B virus (HBV) are limited to Interferon-alpha or the nucleos(t)ide analogs antiviral therapies, and it is crucial to develop and define new antiviral drugs to cure HBV. In this study, we explored the anti-HBV effect of difluoromethylornithine (DFMO), an irreversibly inhibitor of decarboxylase 1(ODC1) on HBV replication. Firstly, we found that polyamines contributed to HBV DNA replication via increasing levels of the HBV core protein (HBc) and capsids. In contrast, depletion of polyamines either by silencing the expression of ODC1 or DFMO treatment, resulted in decreasing viral DNA replication and levels of HBc protein and capsids. Furthermore, we found that DFMO decreased the stability of the HBc protein without affecting mRNA transcription and protein translation. Taken together, our findings demonstrate that DFMO inhibits HBV replication by reducing HBc stability and this may provide a new approach for HBV therapeutics.