title: The Hepatitis B Virus Core Variants that Expose Foreign C-Terminal Insertions on the Outer Surface of Virus-Like Particles.
abstract: The major immunodominant region (MIR) and N-terminus of the hepatitis B virus (HBV) core (HBc) protein were used to expose foreign insertions on the outer surface of HBc virus-like particles (VLPs). The additions to the HBc positively charged arginine-rich C-terminal (CT) domain are usually not exposed on the VLP surface. Here, we constructed a set of recombinant HBcG vectors in which CT arginine stretches were substituted by glycine residues. In contrast to natural HBc VLPs and recombinant HBc VLP variants carrying native CT domain, the HBcG VLPs demonstrated a lowered capability to pack bacterial RNA during expression in Escherichia coli cells. The C-terminal addition of a model foreign epitope from the HBV preS1 sequence to the HBcG vectors resulted in the exposure of the inserted epitope on the VLP surface, whereas the same preS1 sequences added to the native CT of the natural HBc protein remained buried within the HBc VLPs. Based on the immunisation of mice, the preS1 epitope added to the HBcG vectors as a part of preS1(20-47) and preS1phil sequences demonstrated remarkable immunogenicity. The same epitope added to the original C-terminus of the HBc protein did not induce a notable level of anti-preS1 antibodies. HBcG vectors may contribute to the further development of versatile HBc VLP-based vaccine and gene therapy applications.
authors.affiliation: Protein Engineering Department, Latvian Biomedical Research and Study Centre, Ratsupites Str 1, Riga, 1067, Latvia.
authors.forename: Andris
authors.initials: A
authors.lastname: Dishlers
authors.affiliation: Protein Engineering Department, Latvian Biomedical Research and Study Centre, Ratsupites Str 1, Riga, 1067, Latvia.
authors.forename: Dace
authors.initials: D
authors.lastname: Skrastina
authors.affiliation: Protein Engineering Department, Latvian Biomedical Research and Study Centre, Ratsupites Str 1, Riga, 1067, Latvia.
authors.forename: Regina
authors.initials: R
authors.lastname: Renhofa
authors.affiliation: Protein Engineering Department, Latvian Biomedical Research and Study Centre, Ratsupites Str 1, Riga, 1067, Latvia.
authors.forename: Ivars
authors.initials: I
authors.lastname: Petrovskis
authors.affiliation: Protein Engineering Department, Latvian Biomedical Research and Study Centre, Ratsupites Str 1, Riga, 1067, Latvia.
authors.forename: Velta
authors.initials: V
authors.lastname: Ose
authors.affiliation: Protein Engineering Department, Latvian Biomedical Research and Study Centre, Ratsupites Str 1, Riga, 1067, Latvia.
authors.forename: Ilva
authors.initials: I
authors.lastname: Lieknina
authors.affiliation: Protein Engineering Department, Latvian Biomedical Research and Study Centre, Ratsupites Str 1, Riga, 1067, Latvia.
authors.forename: Juris
authors.initials: J
authors.lastname: Jansons
authors.affiliation: Protein Engineering Department, Latvian Biomedical Research and Study Centre, Ratsupites Str 1, Riga, 1067, Latvia.
authors.forename: Paul
authors.initials: P
authors.lastname: Pumpens
authors.affiliation: Protein Engineering Department, Latvian Biomedical Research and Study Centre, Ratsupites Str 1, Riga, 1067, Latvia. Irina@biomed.lu.lv.
authors.forename: Irina
authors.initials: I
authors.lastname: Sominskaya
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D014644:Genetic Variation; D005822:Genetic Vectors; D006510:Hepatitis B Antibodies / Q000097:blood / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D058425:Vaccines, Virus-Like Particle / Q000235:genetics / Q000276:immunology*; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D000939:Epitopes; D006510:Hepatitis B Antibodies; D058425:Vaccines, Virus-Like Particle; D014758:Viral Core Proteins
keywords: C-terminal domain; Core protein; Hepatitis B virus; Immunogenicity; Virus-like particles; preS1 sequence