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Stop codon insertio...
Stop codon insertion restores the particle formation ability of hepatitis B virus core-hantavirus nucleocapsid protein fusions
- Artikel/kapitelEngelska2002
Förlag, utgivningsår, omfång ...
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2003-01-30
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S. Karger AG,2002
Nummerbeteckningar
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:1927869
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http://kipublications.ki.se/Default.aspx?queryparsed=id:1927869URI
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https://doi.org/10.1159/000067927DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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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.
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Lachmann, S
(författare)
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Koletzki, D
(författare)
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Petrovskis, I
(författare)
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Dislers, A
(författare)
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Ose, V
(författare)
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Skrastina, D
(författare)
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Gelderblom, HR
(författare)
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Lundkvist, AKarolinska Institutet
(författare)
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Meisel, H
(författare)
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Borisova, G
(författare)
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Kruger, DH
(författare)
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Pumpens, P
(författare)
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Ulrich, R
(författare)
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Karolinska Institutet
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Intervirology: S. Karger AG45:4-6, s. 340-3490300-55261423-0100
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Till lärosätets databas
- Av författaren/redakt...
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Kazaks, A
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Lachmann, S
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Koletzki, D
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Petrovskis, I
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Dislers, A
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Ose, V
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visa fler...
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Skrastina, D
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Gelderblom, HR
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Lundkvist, A
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Meisel, H
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Borisova, G
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Kruger, DH
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Pumpens, P
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Ulrich, R
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visa färre...
- Artiklar i publikationen
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Intervirology
- Av lärosätet
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Karolinska Institutet