Mechanism to control RNA virus replication and gene expression

A single-stranded RNA virus comprising a modified genome of the virus comprising a polynucleotide sequence encoding protein essential for viral transcription and/or replication, an autocatalytic protease, and a cleavage site for said protease, wherein the single-stranded RNA virus is Vesicular Stomatitis Virus (VSV), the protease is the hepatitis C virus (HCV) NS3 protease or a single chain dimer of the human immunodeficiency virus 1 (HIV-1) protease and the protein essential for viral transcription and/or replication is VSV P-protein or VSV L-protein, wherein

• (a) the protein essential for viral transcription and/or replication comprises an insert at an intramolecular insertion site comprising at least the cleavage site for said protease and further the protease, and wherein the intramolecular insertion site is (i) in the flexible hinge region of the VSV P-protein, or (ii) in the loop of the methyltransferase domain of the L-protein corresponding to amino acids 1614 to 1634 of the amino acid sequence of SEQ ID NO:
• 28;
• or
• (b) the protein essential for viral transcription and/or replication is encoded as a fusion protein comprising the protease fused to the N-terminal end, separated by the cleavage site for said protease, wherein the fusion protein does not comprise the amino acid sequence of SEQ ID NO:
• 30.