APOBEC-Mediated Interference With Hepadnavirus Production

Hepatology, 42, 301-309

Speaker : 張儀君                                   Date : 2005’10’12 14:10~15:00

Commentator : 呂政展 老師                          Place : Room 601

Abstract

APOBEC protein-mediated inhibition of retroviral replication is a powerful mechanism of vertebrate innate immunity. It functions by inducing mutation in retroviral cDNA by cytidine deamination. APOBEC3G is a member of APOBEC protein family, which induces massive C->U deamination of retrovial cDNA, resulting in lethal G->A hypermutation and DNA degradation. Early report described G->A hypermutation in natural HBV variants, raising the question of whether HBV represents another potential target for APOBEC3G. Previous studies have shown that APOBEC3G inhibits HBV DNA production. In the present study, the author performed a detailed mechanistic analysis of the effect of APOBEC3G on HBV DNA production. Not only APOBEC3G but also APOBEC3F inhibit HBV DNA production, although to a lesser extent by APOBEC3F. Although APOBEC3G is a cytidine deaminase, this study showed that the level of core-associated pregnomic RNA was not reduced in the presence of APOBEC3G, however, it rendered the pgRNA more sensitive to micrococcal nuclease digestion. In the presence of APOBEC3G, occasionally these viral DNA and RNA displayed G->A hypermutayions. In conclusion, whether suppression of viral DNA production by cytidine deaminases plays a significant role during natural HBV infection seems speculative at present, because expression of cytidine deaminases in nontransformed liver tissue has not yet been shown. However, a better understanding of mechanisms of APOBEC3G and APOBEC3F interference with HBV production may help identify new therapeutic strategies.

References

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5.      Christine Rosler,et al. APOBEC-Mediated Interference With Hepadnavirus Production. Heptaology, 42, 301-309, 2005