Common localization of retention determinants in hepatitis B virus L protein from different strains.

Hepatitis B virus L protein is retained intracellularly, and trans-inhibits secretion of the related S and M proteins, as particulate HBsAg, at high L/S-M ratios. Comparison of equivalent A and D strain mutants suggested that the retention mechanism does not vary with genotype. Contrary to an earlier suggestion, the N-terminal extension specific for A-C strains was found to be inactive as a retention signal. Intact L was more completely retained than any mutated protein. Retained mutants had either a critical PreS stretch, or N-terminal myristate. Also, mutants of the latter class did not completely inhibit particulate budding, and could, in minor amounts, reach the Golgi. We conclude that (i) the principal retention determinant can be traced to the same PreS segment in distinct strains and (ii) myristic acid does reinforce retention in wild-type L, while acting in part as an HBsAg membrane anchor in mutants lacking the internal determinant.