Modification of virus tropism and host range by viral genome shuffling

A method for generating a viral polynucleotide sequence having a genotype encoding at least one modified viral phenotype, the method comprising:

• contacting a cell or non-human animal which does not naturally support substantial replication of an predetermined virus, with at least one initial infectious virion or replicable genome of said predetermined virus under replication conditions;
• recovering a plurality of replicated genome copies of said predetermined virus, either as virions or as viral genomes in polynucleotide form, wherein some or all of the replicated genome copies comprise a mutation relative to the initial infectious virion or replicable genome;
• recombining a plurality of said replicated genome copies, so as to shuffle the mutations, thereby generating a collection of recombined replicated genome copies;
• and,
• selecting or screening said collection of recombined replicated genome copies to obtain one or more replicable viral genome encoding at least one modified viral phenotype.