Two potentially important elements of the hepatitis B virus large envelope protein are dispensable for the infectivity of hepatitis delta virus

Previous studies have attempted to clarify the roles of the pre-S1 and pre-S2 domains of the large envelope protein of hepatitis B virus (HBV) in attachment and entry into susceptible cells. Difficulties arise in that these domains contain regions involved in the nucleocapsid assembly of HBV and overlapping with the coding regions of the viral polymerase and RNA sequences required for reverse transcription. Such difficulties can be circumvented with hepatitis delta virus (HDV), which needs the HBV large envelope protein only for infectivity. Thus, mutated HBV envelope proteins were examined for their effects on HDV infectivity. Changing the C-terminal region of pre-S1 critical for HBV assembly allowed the envelopment of HDV and had no effect on infectivity in primary human hepatocytes. Similarly, a deletion of the 12 amino acids of a putative translocation motif (TLM) in pre-S2 had no effect. Thus, these two regions are not necessary for HDV infectivity and, by inference, are not needed for HBV attachment and entry into susceptible cells.