Acetylation of Delta Antigen

HDV replication takes place within the nucleus (Rizzetto et al. 1977; Wu et al. 1992). However, both HDAg and genomic HDV RNA can be found in the cytoplasm (Macnaughton and Lai 2002). Kinetic studies of newly synthesized HDV RNA in heterokaryons indicated a transient phase of shuttling viral genomic RNA into the cytoplasm and then re-importing into the nucleus

(Tavanez et al. 2002), indicating the importance of nucleocytoplasmic shuttling in the HDV life cycle. We have demonstrated that acetylation of S-HDAg may be a signal responsible for modulating such shuttling. Both isoforms of HDAg are acetylated, and lysine 72 (K72) of S-HDAg was identified as one of the acetylation sites (Mu et al. 2004). Substitution of K72 by arginine (K72R) caused the S-HDAg mutant to redistribute from the nucleus to the cytoplasm. The K72R mutant also reduced genomic RNA synthesis from antigenomic RNA template and resulted in the earlier appearance of L-HDAg. These results demonstrated that HDAg is an acetylated protein and acetylation on K72 of S-HDAg may modulate the subcellular localization of S-HDAg and participate in viral RNA nucleocytoplasmic shuttling and replication.

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