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APOBEC-mediated interference with hepadnavirus production.
Christine Rösler1, Josef Köck, Michael Kann
1Department of Medicine II, University of Freiburg, Germany.
Hepatology (Baltimore, Md.)
|July 19, 2005
Summary
The apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G (APOBEC3G) and APOBEC3F suppress hepatitis B virus (HBV) production. However, APOBEC3G/3F-mediated nucleic acid editing is not an effective defense against hepadnaviruses.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- APOBEC3G is a cellular enzyme with known antiretroviral activity.
- Previous studies indicated APOBEC3G suppresses hepatitis B virus (HBV) production in human hepatoma cells.
Purpose of the Study:
- To investigate the mechanisms of APOBEC-mediated antiviral activity against HBV and related hepadnaviruses.
- To determine if APOBEC3G/3F-mediated nucleic acid editing serves as an innate defense against hepadnaviruses.
Main Methods:
- Assessed the effect of human APOBEC3G and APOBEC3F on HBV production in various cell types.
- Analyzed viral morphogenesis, RNA and protein synthesis, and reverse-transcription.
- Investigated the role of HBV X protein in APOBEC-mediated antiviral activity.
- Examined nucleic acid mutations in viral particles produced in the presence of APOBEC proteins.
Main Results:
- Human APOBEC3G effectively blocked HBV production in mammalian and nonmammalian cells, including duck HBV.
- APOBEC3G destabilized HBV pregenomic RNA within core protein capsids, but did not inhibit reverse-transcription.
- HBV X protein did not modulate the antiviral effect of APOBEC3G.
- Human APOBEC3F inhibited HBV DNA production, with occasional mutations observed in viral RNA and DNA, unlike rat APOBEC1.
Conclusions:
- APOBEC3G and APOBEC3F can downregulate the production of replication-competent hepadnaviral nucleocapsids.
- Unlike retroviruses, APOBEC3G/3F-mediated nucleic acid editing is not a significant innate defense mechanism against hepadnaviruses.