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Different antiviral activities of natural APOBEC3C, APOBEC3G, and APOBEC3H variants against hepatitis B virus

Arun Kanagaraj1, Naoya Sakamoto1, Lusheng Que2

  • 1Department of Molecular Genetics, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

Biochemical and Biophysical Research Communications
|August 12, 2019
PubMed

Insights

Certain APOBEC3 variants show potential in fighting Hepatitis B virus (HBV). Specific variants of APOBEC3C and APOBEC3H demonstrated enhanced restriction and hypermutation activity against HBV DNA, suggesting a role in viral clearance.

Area of Science:

  • Virology
  • Immunology
  • Genetics

Background:

  • Hepatitis B virus (HBV) causes severe liver disease, including cirrhosis and hepatocellular carcinoma.
  • The APOBEC3 (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3) family includes proteins with known antiviral properties against DNA and retroviruses.

Purpose of the Study:

  • To investigate the differential anti-HBV activities of natural human APOBEC3C, APOBEC3G, and APOBEC3H variants.
  • To identify specific APOBEC3 genetic variations that influence the restriction and hypermutation of HBV DNA.

Main Methods:

  • Utilized an HBV-replicating cell culture model to assess antiviral activity.
  • Evaluated natural variants of APOBEC3C, APOBEC3G, and APOBEC3H, including polymorphisms and splicing variants of APOBEC3H.
  • Quantified restriction activity and hypermutation frequency against HBV DNA.

Main Results:

  • The APOBEC3C variant S188I exhibited increased restriction activity and hypermutation frequency against HBV.
  • The APOBEC3G variant H186R showed no significant change in anti-HBV or hypermutation activities.
  • Among APOBEC3H variants, hap II SV-183 demonstrated the most potent restriction activity against HBV.

Conclusions:

  • Genetic variations within APOBEC3 genes can modulate their efficacy in restricting HBV replication.
  • Specific APOBEC3C and APOBEC3H variants possess enhanced antiviral properties against HBV, offering potential therapeutic targets.
  • These findings highlight the importance of host genetic factors in controlling HBV infection and disease progression.

Keywords:
APOBECAntiviral proteinCytidine deaminaseHepatitis B virus

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