VIRUSES DEPENDENT ON INDUCING AGENTS FOR VIRAL ENTRY INTO A HOST CELL

摘要

The invention provides a method for rendering a virus dependent on an inducing agent for viral entry by means of a pairing of two domains (HR1 and HR2) of an envelope glycoprotein into a host cell, wherein said inducing agent is capable of interfering in said pairing, comprising increasing the affinity between a HR1 domain and a HR2 domain of said envelope glycoprotein of said virus to such extent that said pairing occurs without the presence of a host cell (a premature switch) when said inducing agent is essentially not present. Preferably, said inducing agent comprises a peptide fusion inhibitor or a chaotrophic agent. A virus dependent on an inducing agent for viral entry is also herewith provided, as well as a viral replicon comprising a nucleic acid sequence with a mutation in a region encoding an HR1 domain and/or HR2 domain of an envelope glycoprotein, resulting in an increased affinity between said HR1 domain and said HR2 domain to such extent that pairing of said HR1 and HR2 domains occurs without the presence of a host cell when an inducing agent is essentially not present. A vaccine comprising said virus and/or viral replicon is also provided.