內科CHEN, DING-SHINNDING-SHINNCHEN陳培哲2008-12-292018-07-112008-12-292018-07-112001http://ntur.lib.ntu.edu.tw//handle/246246/95160Hepatitis delta virus (HDV) small delta antigen (S-HDAg) plays a critical role in virus replication. We previously demonstrated that the S-HDAg phospholylation occurs on both serine and threonine residues. However, their biological significance and the exact phosphorylation sites of S- HDAg are still unknown. In this study, phosphorylated S-HDAg was detected only in the intracellular compartment, not in viral particles. In addition , the number of phospholylated isoforms of S-HDAg significantly increased with the extent of viral replication in transfection system. Site-directed mutagenesis showed that alanine replacement of serine 177, which is conserved among all the known HDV strains, resulted in reduced phosphorylation of S-HDAg, while the mutation of the other two conserved serine residues (2 and 123) had little effect. The S177A mutant dramatically decreased its capability in assisting HDV RNA replication, with a preferential and profound impairment of the antigenomic RNA replication. Furthermore, the viral RNA editing, a step relying upon antigenomic RNA replication, was also abolished by this mutation. These results suggested that phosphorylation of S-HDAg, with serine 177 as a presumable site, plays a critical role in viral RNA replication, especially in augmenting the replication of antigenomic RNA.en-USPROTEIN-KINASE-CB SURFACE-ANTIGENMOLECULAR-CLONINGTRANSCRIPTIONGENOMEPHOSPHOPROTEIN[SDGs]SDG3journal article