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Posttranslational modifications and secretion efficiency of immunogenic hepatitis B virus L protein deletion variants

Baiba Niedre-Otomere1*, Ance Bogdanova1, Ruta Bruvere1, Velta Ose1, Wolfram H Gerlich2, Paul Pumpens1, Dieter Glebe2 and Tatjana Kozlovska1

Author Affiliations

1 Biomedical Research and Study Centre, Ratsupites street 1, LV-1067, Riga, Latvia

2 Institute of Medical Virology, Justus Liebig University, Schubertstr. 81, D-35392, Giessen, Germany

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Virology Journal 2013, 10:63  doi:10.1186/1743-422X-10-63

Published: 25 February 2013



Subviral particles of hepatitis B virus (HBV) composed of L protein deletion variants with the 48 N-terminal amino acids of preS joined to the N-terminus of S protein (1-48preS/S) induced broadly neutralizing antibodies after immunization of mice with a Semliki Forest virus vector. A practical limitation for use as vaccine is the suboptimal secretion of such particles. The role of the N-terminal preS myristoylation in the cellular retention of full-length L protein is described controversially in the literature and the relation of these data to the truncated L protein was unknown. Thus, we studied the effect of preS myristoylation signal suppression on 1-48preS/S secretion efficiency, glycosylation and subcellular distribution.


The findings are that 1-48preS/S is secreted, and that removal of the N-terminal myristoylation signal in its G2A variant reduced secretion slightly, but significantly. The glycosylation pattern of 1-48preS/S was not affected by the removal of the myristoylation signal (G2A mutant) but was different than natural L protein, whereby N4 of the preS and N3 of the S domain were ectopically glycosylated. This suggested cotranslational translocation of 1-48preS in contrast to natural L protein. The 1-48preS/S bearing a myristoylation signal was localized in a compact, perinuclear pattern with strong colocalization of preS and S epitopes, while the non-myristoylated mutants demonstrated a dispersed, granular cytoplasmic distribution with weaker colocalization.


The large deletion in 1-48preS/S in presence of the myristoylation site facilitated formation and secretion of protein particles with neutralizing preS1 epitopes at their surface and could be a useful feature for future hepatitis B vaccines.

L protein; PreS1 domain; N-terminal myristoylation; Secretion; Glycosylation