| 摘要 |
<p>The present invention relates to viruses containing glycoproteins with furin binding sites. For BRSV it has been found that the 27AA IFCSP is not essential for cell fusion activity of the F protein and the deletion or replacement of at least part of the IFCSP does not destroy F function for productive BRSV replication. Removal of Gly110 to Arg 136 and transient expression of the resulting protein (Fins) resulted in formation of syncitia which were slightly smaller that those induced by wt F. thus, it has been found that oligopeptides, or bioactive proteins, can be integrated between 2 furin cleavage sites of a carrier glycoprotein, such as the furin cleavage sites of an F protein of an RSV. Due to the processing of the precursor protein, resulting in the cleavage at the furin cleavage sites, the heterologous sequence may be excised and consequently be secreted by a virus-infected cell. This concept can be applied likewise to other glycoproteins containing two furin cleavage sites, where the original sequence between the cleavage sites may replaced (in part) by a heterologous sequence or may simply be deleted. In proteins with one furin cleavage site, heterologous sequences may be inserted together with the sequence for a second cleavage site, thus creating a situation where the heterologous sequence is again flanked by two furin cleavage sites in the recombinant protein. Processing of the mutated protein will than also result in the excision of the heterologous sequence which may be secreted by virus infected cells. Viruses wherein glycoproteins are modified in one of the above-described ways, can be used for, for example vaccine purposes.</p> |
