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Posttranslational modifications and secretion efficiency of immunogenic hepatitis B virus L protein deletion variants
BACKGROUND: 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 pra...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598826/ https://www.ncbi.nlm.nih.gov/pubmed/23442390 http://dx.doi.org/10.1186/1743-422X-10-63 |
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author | Niedre-Otomere, Baiba Bogdanova, Ance Bruvere, Ruta Ose, Velta Gerlich, Wolfram H Pumpens, Paul Glebe, Dieter Kozlovska, Tatjana |
author_facet | Niedre-Otomere, Baiba Bogdanova, Ance Bruvere, Ruta Ose, Velta Gerlich, Wolfram H Pumpens, Paul Glebe, Dieter Kozlovska, Tatjana |
author_sort | Niedre-Otomere, Baiba |
collection | PubMed |
description | BACKGROUND: 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. FINDINGS: 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. CONCLUSIONS: 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. |
format | Online Article Text |
id | pubmed-3598826 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35988262013-03-16 Posttranslational modifications and secretion efficiency of immunogenic hepatitis B virus L protein deletion variants Niedre-Otomere, Baiba Bogdanova, Ance Bruvere, Ruta Ose, Velta Gerlich, Wolfram H Pumpens, Paul Glebe, Dieter Kozlovska, Tatjana Virol J Short Report BACKGROUND: 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. FINDINGS: 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. CONCLUSIONS: 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. BioMed Central 2013-02-25 /pmc/articles/PMC3598826/ /pubmed/23442390 http://dx.doi.org/10.1186/1743-422X-10-63 Text en Copyright ©2013 Niedre-Otomere et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Short Report Niedre-Otomere, Baiba Bogdanova, Ance Bruvere, Ruta Ose, Velta Gerlich, Wolfram H Pumpens, Paul Glebe, Dieter Kozlovska, Tatjana Posttranslational modifications and secretion efficiency of immunogenic hepatitis B virus L protein deletion variants |
title | Posttranslational modifications and secretion efficiency of immunogenic hepatitis B virus L protein deletion variants |
title_full | Posttranslational modifications and secretion efficiency of immunogenic hepatitis B virus L protein deletion variants |
title_fullStr | Posttranslational modifications and secretion efficiency of immunogenic hepatitis B virus L protein deletion variants |
title_full_unstemmed | Posttranslational modifications and secretion efficiency of immunogenic hepatitis B virus L protein deletion variants |
title_short | Posttranslational modifications and secretion efficiency of immunogenic hepatitis B virus L protein deletion variants |
title_sort | posttranslational modifications and secretion efficiency of immunogenic hepatitis b virus l protein deletion variants |
topic | Short Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598826/ https://www.ncbi.nlm.nih.gov/pubmed/23442390 http://dx.doi.org/10.1186/1743-422X-10-63 |
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