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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003269naa a2200409 4500
001oai:prod.swepub.kib.ki.se:1927869
003SwePub
008240701s2002 | |||||||||||000 ||eng|
024a http://kipublications.ki.se/Default.aspx?queryparsed=id:19278692 URI
024a https://doi.org/10.1159/0000679272 DOI
040 a (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
100a Kazaks, A4 aut
2451 0a Stop codon insertion restores the particle formation ability of hepatitis B virus core-hantavirus nucleocapsid protein fusions
264 c 2003-01-30
264 1b S. Karger AG,c 2002
520 a In recent years, epitopes of various origin have been inserted into the core protein of hepatitis B virus (HBc), allowing the formation of chimeric HBc particles. Although the C-terminus of a C-terminally truncated HBc (HBcΔ) tolerates the insertion of extended foreign sequences, the insertion capacity is still a limiting factor for the construction of multivalent vaccines. Previously, we described a new system to generate HBcΔ mosaic particles based on a read-through mechanism in an <i>Escherichia coli</i> suppressor strain [J Gen Virol 1997;78:2049–2053]. Those mosaic particles allowed the insertion of a 114-amino acid (aa)-long segment of a Puumala hantavirus (PUUV) nucleocapsid (N) protein. To study the value and the potential limitations of the mosaic approach in more detail, we investigated the assembly capacity of ‘non-mosaic’ HBcΔ fusion proteins and the corresponding mosaic constructs carrying 94, 213 and 433 aa of the hantaviral N protein. Whereas the fusion proteins carrying 94, 114, 213 or 433 aa were not assembled into HBcΔ particles, or only at a low yield, the insertion of a stop codon-bearing linker restored the ability to form particles with 94, 114 and 213 foreign aa. The mosaic particles formed exhibited PUUV-N protein antigenicity. Immunization of BALB/c mice with these mosaic particles carrying PUUV-N protein aa 1–114, aa 1–213 and aa 340–433, respectively, induced HBc-specific antibodies, whereas PUUV-N protein-specific antibodies were detected only in mice immunized with particles carrying N-terminal aa 1–114 or aa 1–213 of the N protein. Both the anti-HBc and anti-PUUV antibody responses were IgG1 dominated. In conclusion, stop codon suppression allows the formation of mosaic core particles carrying large-sized and ‘problematic’, e.g. hydrophobic, hantavirus sequences.
700a Lachmann, S4 aut
700a Koletzki, D4 aut
700a Petrovskis, I4 aut
700a Dislers, A4 aut
700a Ose, V4 aut
700a Skrastina, D4 aut
700a Gelderblom, HR4 aut
700a Lundkvist, Au Karolinska Institutet4 aut
700a Meisel, H4 aut
700a Borisova, G4 aut
700a Kruger, DH4 aut
700a Pumpens, P4 aut
700a Ulrich, R4 aut
710a Karolinska Institutet4 org
773t Intervirologyd : S. Karger AGg 45:4-6, s. 340-349q 45:4-6<340-349x 0300-5526x 1423-0100
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:1927869
8564 8u https://doi.org/10.1159/000067927

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