The Hypothesis

We propose that the delta antigens are modified post-translationally to produce many different isoforms. Although the amino acid backbone remains unchanged, the modified delta antigens can exert different functions in the viral replication cycle in different subcelluar compartments. Perhaps the post-translational modifications (PTMs) of proteins can draw a similarity with dressing codes for humans. A person has to perform multiple social functions on different occasions, for which the person has to put on different but appropriate costumes. In this way, the same person enriches the life and expands one's social capacity. In a similar fashion, for delta antigen, different PTMs produce uniquely modified delta isoforms that recognizes the right cellular compartment and interacting partners to conduct the requested activity.

There are already many precedents for PTMs altering the functional capacity of delta antigens. Many proteins interacting with nucleic acids frequently adopt this strategy. Eukaryotic chromosomal packing or modeling proteins, such as histones, rely on PTM to reversibly modulate their interaction with the genome. Transcriptional factors, such as NFkB, traffic between the cytoplasm and the nucleus by differential acetylation. Drawing from these cases, delta antigens may undergo different PTMs in order to transform into distinct isoforms to conduct the required functions at successive stages of the HDV life cycle.

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