Soluble receptor-mediated targeting of mouse hepatitis coronavirus to the human epidermal growth factor receptor.
J Virol
; 79(24): 15314-22, 2005 Dec.
Article
em En
| MEDLINE
| ID: mdl-16306602
ABSTRACT
The mouse hepatitis coronavirus (MHV) infects murine cells by binding of its spike (S) protein to murine CEACAM1a. The N-terminal part of this cellular receptor (soR) is sufficient for S binding and for subsequent induction of the conformational changes required for virus-cell membrane fusion. Here we analyzed whether these characteristics can be used to redirect MHV to human cancer cells. To this end, the soR domain was coupled to single-chain monoclonal antibody 425, which is directed against the human epidermal growth factor receptor (EGFR), resulting in a bispecific adapter protein (soR-425). The soR and soR-425 proteins, both produced with the vaccinia virus system, were able to neutralize MHV infection of murine LR7 cells. However, only soR-425 was able to target MHV to human EGFR-expressing cancer cells. Interestingly, the targeted infections induced syncytium formation. Furthermore, the soR-425-mediated infections were blocked by heptad repeat-mimicking peptides, indicating that virus entry requires the regular S protein fusion process. We conclude that the specific spike-binding property of the CEACAM1a N-terminal fragment can be exploited to direct the virus to selected cells by linking it to a moiety able to bind a receptor on those cells. This approach might be useful in the development of tumor-targeted coronaviruses.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
/
Proteínas do Envelope Viral
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Infecções por Coronavirus
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Vírus da Hepatite Murina
/
Receptores ErbB
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Virol
Ano de publicação:
2005
Tipo de documento:
Article