Mu J.-J.Tsay Y.-G.Juan L.-J.Fu T.-F.Huang W.-H.Chen D.-S.PEI-JER CHEN2021-07-032021-07-0320040042-6822https://www.scopus.com/inward/record.uri?eid=2-s2.0-84983719289&doi=10.1016%2fj.virol.2003.10.024&partnerID=40&md5=400ff5693ad64889e9bc9956d3d7b633https://scholars.lib.ntu.edu.tw/handle/123456789/568724Hepatitis delta virus (HDV) is a single-stranded RNA virus that encodes two viral nucleocapsid proteins named small and large form hepatitis delta antigen (S-HDAg and L-HDAg). The S-HDAg is essential for viral RNA replication while the L-HDAg is required for viral assembly. In this study, we demonstrated that HDAg are acetylated proteins. Metabolic labeling with [3H] acetate revealed that both forms of HDAg could be acetylated in vivo. The histone acetyltransferase (HAT) domain of cellular acetyltransferase p300 could acetylate the full-length and the N-terminal 88 amino acids of S-HDAg in vitro. By mass spectrometric analysis of the modified protein, Lys-72 of S-HDAg was identified as one of the acetylation sites. Substitution of Lys-72 to Arg caused the mutant S-HDAg to redistribute from the nucleus to the cytoplasm. The mutant reduced viral RNA accumulation and resulted in the earlier appearance of L-HDAg. These results demonstrated that HDAg is an acetylated protein and mutation of HDAg at Lys-72 modulates HDAg subcellular localization and may participate in viral RNA nucleocytoplasmic shuttling and replication. ? 2003 Elsevier Inc. All rights reserved.Acetylation; HDAg; HDV; NLS; p300[SDGs]SDG3acetic acid; acyltransferase; amino acid; arginine; histone acetyltransferase; lysine; mutant protein; protein p300; protein subunit; tritium; virus antigen; virus RNA; acetylation; amino acid substitution; amino terminal sequence; article; cell nucleus; controlled study; cytoplasm; Hepatitis delta virus; human; human cell; in vitro study; in vivo study; isotope labeling; mass spectrometry; metabolism; nonhuman; priority journal; protein domain; protein function; protein localization; RNA synthesis; Hepatitis delta virus; RNA virusesjournal article10.1016/j.virol.2003.10.024149674882-s2.0-84983719289