Relating structure to function in the hepatitis delta virus antigen

D W Lazinski, J M Taylor
1993 Journal of Virology  
Hepatitis delta virus expresses two forms of a single protein, the small (BAg-S) and large (bAg-L) antigens, which are identical except for an additional 19 residues present at the C terminus of bAg-L. While bAg-S is required to promote genome replication, bAg-L potently inhibits this process and also facilitates packaging of the viral genome by envelope proteins of the helper virus (hepatitis B virus). Regions within the antigens responsible for nuclear localization, RNA binding, and
more » ... on have been identified, yet it is not clear how these particular activities contribute to the ultimate replication and packaging phenotypes. Here we report the following findings. (i) Although the removal of the nuclear localization signal from either antigen resulted in significant cytoplasmic accumulation, both proteins still had access to the nucleus. As a consequence, no functional defect was observed with either mutant. (ii) The RNA-binding domain, although necessary for bAg-S function, could be deleted from bAg-L without compromising its ability to either inhibit replication or promote packaging. (iii) In contrast, the coiled-coil dimerization domain was required for both the activation of replication by bAg-S and the inhibition of replication by bAg-L. This region, with an additional 20 amino acids C-terminal to it, was necessary and sufficient to potently inhibit replication by interacting with the small antigen. (iv) The packaging property of bAg-L required a C-terminal Pro/Gly-rich region which is hypothesized to interact with the hepatitis B virus envelope proteins during the assembly process. * Corresponding author. unable to support genome replication, but it acts as a trans-dominant inhibitor of this process. When bAg-L is expressed to only 1/10 the level of bAg-S, the number of essential activity required for the function of bAg-S, this has not yet been established experimentally, and the importance of this region to the phenotypes of bAg-L is unknown. An adjacent region, a.a. 67 to 88, constitutes the nuclear localization signal (NLS) (33). Residues 69 to 75 can be
doi:10.1128/jvi.67.5.2672-2680.1993 fatcat:6w5dhkzrt5ai3l3jzaxu2jp5zi