Abstract: The present invention relates to a novel mechanism to control RNA virus replication and gene expression using a conditional protease approach using a specific protease inhibitor for regulation. More specifically it relates to a single-stranded RNA virus, preferably of the order Mononegavirales, comprising a polynucleotide sequence encoding at least one protein essential for viral transcription and/or replication, a protease and a cleavage site for said protease. The protease can be inhibited using a protease inhibitor and hence the protease and the cleavage site for said protease form a regulatable switch. By changing the insertion site of the regulatable switch from an INTRA- to an INTER-molecular location in the at least one protein essential for viral transcription and/or replication, the effect of the protease inhibitor can be altered from an ON switch to an OFF switch. RNA virus may further encode a heterologous protein, the expression of which is then regulated by regulating viral activity.

Abstract: The invention relates to gene therapy of HIV infection by providing to a patient a nucleic acid for the expression of in vivo secretable peptides that prevent entry of the virus into the cell. The invention makes available nucleic acids and vectors containing the same that code for a fusion protein which contains two HIV entry inhibitory peptides which are connected by a cleavable linker, wherein the peptides are preferably derived from the second (C) heptad repeat of the gp41 protein of HIV.