2. Academic Validation
  3. Compound IMB-Z inhibits hepatitis B virus replication through increasing APOBEC3G expression and incorporation into viral nucleocapsids

Compound IMB-Z inhibits hepatitis B virus replication through increasing APOBEC3G expression and incorporation into viral nucleocapsids

  • J Glob Antimicrob Resist. 2022 Nov 14;S2213-7165(22)00250-8. doi: 10.1016/j.jgar.2022.11.006.
Jin Hu 1,  Huiqiang Wang 1,  Lu Yang 1,  Shuo Wu 2,  Yanping Li 3,  Yuhuan Li 4,  Zhuorong Li 5
Affiliations

Affiliations

  • 1 CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.; Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.; NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • 2 CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.; Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.; NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.. Electronic address: wushuoimb@126.com.
  • 3 CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.. Electronic address: liyanping@imb.pumc.edu.cn.
  • 4 CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.; Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.; NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.. Electronic address: yuhuanlibj@126.com.
  • 5 CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
PMID: 36396043 DOI: 10.1016/j.jgar.2022.11.006
Abstract

Background: 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 (EV71) 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 were detected 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 EV71 replication, we found that IMB-Z's inhibition of HBV replication is associated with increased level of A3G. Mechanistically, we demonstrated that the inhibitory effect of IMB-Z is independent on 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.

Keywords

APOBEC3G; IMB-Z; hepatitis B virus; incorporation.

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