1887

Abstract

APOBEC3 cytidine deaminases hypermutate hepatitis B virus (HBV) and inhibit its replication . Whether this inhibition is due to the generation of hypermutations or to an alternative mechanism is controversial. A series of APOBEC3B (A3B) point mutants was analysed for hypermutational activity on HBV DNA and for inhibitory effects on HBV replication. Point mutations inactivating the carboxy-terminal deaminase domain abolished the hypermutational activity and reduced the inhibitory activity on HBV replication to approximately 40 %. In contrast, the point mutation H66R, inactivating the amino-terminal deaminase domain, did not affect hypermutations, but reduced the inhibition activity to 63 %, whilst the mutant C97S had no effect in either assay. Thus, only the carboxy-terminal deaminase domain of A3B catalyses cytidine deaminations leading to HBV hypermutations, but induction of hypermutations is not sufficient for full inhibition of HBV replication, for which both domains of A3B must be intact.

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2007-12-01
2019-11-12
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vol. , part 12, pp. 3270 – 3274

A selection of unique hypermutated HBV sequences from HuH-7 cells expressing A3B wild-type, H66R, C97S or H66R/C97S mutant, shown in comparison to the reference sequence of the viral (+) strand [ PDF] (41 KB)



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