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Dual effect of APOBEC3G on Hepatitis B virus

¹ Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima-shi 734-8551, Japan
² Liver Research Project Center, Hiroshima University, Hiroshima, Japan
³ Laboratory for Liver Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Yokohama 230-0045, Japan
⁴ Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
⁵ Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan

Correspondence
Kazuaki Chayama
chayama{at}hiroshima-u.ac.jp

G to A hypermutation of Hepatitis B virus (HBV) and retroviruses appears as a result of deamination activities of host APOBEC proteins and is thought to play a role in innate antiviral immunity. Alpha and gamma interferons (IFN- and -) have been reported to upregulate the transcription of APOBEC3G, which is known to reduce the replication of HBV. We investigated the number of hypermutated genomes under various conditions by developing a quantitative measurement. The level of hypermutated HBV in a HepG2 cell line, which is semi-permissive for retrovirus, was 2.3 in 10⁴ HBV genomes, but only 0.5 in 10⁴ in permissive Huh7 cells. The level of APOBEC3G mRNA was about ten times greater in HepG2 cells than in Huh7 cells. Treatment of HepG2 cells with either IFN- or - increased the transcription of APOBEC3G and hypermutation of HBV. These mRNAs and hypermutation of HBV genomes were induced more prominently by IFN- than by IFN-. Both IFNs decreased the number of replicative intermediate of HBV. Overexpression of APOBEC3G reduced the number of replicative intermediate of HBV and increased hypermutated genomes 334 times, reaching 968 in 10⁴ genomes. Deamination-inactive APOBEC3G did not induce hypermutation, but reduced the virus equally. Our results suggest that APOBEC3G, upregulated by IFNs, has a dual effect on HBV: induction of hypermutation and reduction of virus synthesis. The effect of hypermutation on infectivity should be investigated further.

This article has been cited by other articles:

				J. Kock and H. E. Blum Hypermutation of hepatitis B virus genomes by APOBEC3G, APOBEC3C and APOBEC3H J. Gen. Virol., May 1, 2008; 89(5): 1184 - 1191. [Abstract] [Full Text] [PDF]