Provided are recombinant viral genomes. The viral genomes find use in a variety of contexts including for the production of viruses effective in inducing death of cells exhibiting a signal specific to a disease or disorder in a subject, where the viral life cycle is dependent upon the signal specific to the disease or disorder. According to some embodiments, the viral genomes comprise one or more transcription units comprising a sequence encoding a first fusion protein comprising a protease and a first binding domain that binds to a first target, and a sequence encoding a second fusion protein comprising a membrane-targeting signal, a second binding domain that binds to a second target, a cleavable substrate for the protease, and either a transcriptional effector protein or viral protein encoded by a viral gene deleted in the viral genome. Also provided are related cells, virions, pharmaceutical compositions and methods of use.

The invention relates to an isolated non-naturally occurring protein comprising the amino acid sequence as set forth in SEQ ID NO: 1, and wherein the amino acid in position 8, 47, 209 and/or 354 is substituted by any amino acid different from the amino acid indicated at that position in said sequence SEQ ID NO: 1.

The invention relates to an isolated non-naturally occurring protein comprising the amino acid sequence as set forth in SEQ ID NO: 1, and wherein the amino acid in position 8, 47, 209 and/or 354 is substituted by any amino acid different from the amino acid indicated at that position in said sequence SEQ ID NO: 1.

The invention relates to an isolated non-naturally occurring protein comprising the amino acid sequence as set forth in SEQ ID NO: 1, and wherein the amino acid in position 8, 47, 209 and/or 354 is substituted by any amino acid different from the amino acid indicated at that position in said sequence SEQ ID NO: 1.