Casein kinase II and protein kinase C modulate hepatitis delta virus RNA replication but not empty viral particle assembly

摘要: Hepatitis delta virus (HDV) contains two virus-specific antigens (HDAgs), large and small forms, which are identical in sequence except that the one 19 extra amino acids at C terminus. HDAgs nuclear phosphoproteins with distinct biological functions; form activates HDV RNA replication, whereas suppresses this process but is required for viral particle assembly. In study, we have characterized phosphorylative property of HDAg a human hepatoma cell line (HuH-7) examined role phosphorylation function. As demonstrated by vivo labeling kinase inhibitor experiments, levels both were diminished casein II (CKII). Nevertheless, only could be markedly reduced protein (PKC) inhibitor, suggesting different properties between HDAgs. When these inhibitors added separately to transient-expression system, replication was profoundly suppressed. contrast, did not affect assembly empty from hepatitis B surface antigen. To further examine function, conservative CKII recognition sites Ser-2 Ser-123 potential PKC site Ser-210 altered alanine site-directed mutagenesis. Transfection experiments indicated mutation Ser-2, Ser-123, significantly impaired activity assisting replication. This accordance our observation predominant HDAg. Our studies also excluded possibility or Ser-210, had roles trans-suppression HDAg, virus-like particle, transport conclusion, results indicate positively modulate particle. The may least part accounted effect on is, however, mediate rather act as-yet-unidentified Ser Thr residues cellular factors. These findings provide first insight into cycle.