1. Compound IMB-Z inhibits hepatitis B virus replication through increasing APOBEC3G expression and incorporation into viral nucleocapsids.
- Author
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Hu J, Wang H, Yang L, Wu S, Li Y, Li Y, and Li Z
- Subjects
- Humans, Cytidine Deaminase genetics, Cytidine Deaminase metabolism, Cytidine Deaminase pharmacology, Nucleocapsid genetics, Nucleocapsid metabolism, Virus Replication, Antiviral Agents chemistry, Antiviral Agents pharmacology, APOBEC-3G Deaminase drug effects, APOBEC-3G Deaminase genetics, Hepatitis B drug therapy, Hepatitis B virus genetics
- Abstract
Objectives: As a host restriction factor, apolipoprotein B messenger RNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G or A3G) has been shown to suppress the replication of several viruses including hepatitis B virus (HBV). Recently, we reported that IMB-Z, a N-phenylbenzamide derivative, could inhibit Enterovirus 71 replication, and A3G mediated its antiviral activity. Whether IMB-Z exhibits an inhibitory effect on HBV replication has not been investigated., Material and Methods: HBV DNA, pregenomic RNA (pgRNA), core protein, and capsid levels were determined by a qPCR assay or Southern blot, Northern blot, Western blot, and particle gel assay, respectively. Mutation analysis of HBV DNAs was conducted by a differential DNA denaturation PCR assay. A3G encapsidation into HBV nucleocapsids was examined by Western blot analysis after ultracentrifugation and a co-immunoprecipitation (IP) assay between HBV core and A3G proteins., Results: In the present study, we found that IMB-Z could considerably inhibit HBV replication in HepAD38 cells. Interestingly, IMB-Z did not alter the HBV pgRNA production but could reduce the level of core protein, viral nucleocapsids, and core-associated DNA, as well as cccDNA intracellular amplification. Similar to the action of IMB-Z's inhibition of Enterovirus 71 replication, we found that IMB-Z's inhibition of HBV replication was associated with increased level of A3G. Mechanistically, we demonstrated that the inhibitory effect of IMB-Z is independent of the cytidine deaminase activity of A3G and is exerted by increasing its incorporation into viral nucleocapsids., Conclusions: Our results indicate that IMB-Z inhibits HBV through pharmacological induction A3G expression and incorporation into HBV nucleocapsids., Competing Interests: Competing interests None declared., (Copyright © 2022 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
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