The application generally relates to the attenuation of a RNA virus or of a clone thereof and involves the alteration of sequence space, more particularly the reduction, of mutational robustness of said RNA virus or clone. The means of the application are more particularly dedicated to the attenuation of an infectious RNA virus or clone, for the production of immunogenic composition or vaccine. More particularly, the means of the application involve the replacement of codon(s) by different codon(s), which is(are) selected to differ by only one nucleotide from a codon STOP, more particularly by different but synonymous codon(s), which is(are) selected to differ by only one nucleotide from a codon STOP.

An attenuated strain of cucumber green mottle mosaic virus (CGMMV) is useful to protect cucumber plants from infection with the wild-type infectious CGMMV strain. The genome of the attenuated virus contains at least one mutation or group of mutations selected from c.4969G>A, c.3334C>T, and a group of at least six of the mutations c.315G>A; c.1498A>G; c.1660C>T; c.3430C>T; c.3528A>G; c.4144C>T; c.4248C>T; and c.6228C>T. These mutated genomes encode one or more mutations selected from R163711 in the 186 kDa readthrough replication protein, A1092V in the 129 kDa replication protein and/or the 186 kDa readthrough replication protein, and at least six mutations selected from G86S, E480G, S534F, A1124V, N1157D, P1362L, P1397S in the 129 kDa replication protein and/or the 186 kDa readthrough replication protein, and the A156V mutation in the coat protein.

An attenuated strain of cucumber green mottle mosaic virus (CGMMV) is useful to protect cucumber plants from infection with the wild-type infectious CGMMV strain. The genome of the attenuated virus contains at least one mutation or group of mutations selected from c.4969G>A, c.3334C>T, and a group of at least six of the mutations c.315G>A; c.1498A>G; c.1660C>T; c.3430C>T; c.3528A>G; c.4144C>T; c.4248C>T; and c.6228C>T. These mutated genomes encode one or more mutations selected from R163711 in the 186 kDa readthrough replication protein, A1092V in the 129 kDa replication protein and/or the 186 kDa readthrough replication protein, and at least six mutations selected from G86S, E480G, S534F, A1124V, N1157D, P1362L, P1397S in the 129 kDa replication protein and/or the 186 kDa readthrough replication protein, and the A156V mutation in the coat protein.

An attenuated strain of cucumber green mottle mosaic virus (CGMMV) is useful to protect cucumber plants from infection with the wild-type infectious CGMMV strain. The genome of the attenuated virus contains at least one mutation or group of mutations selected from c.4969G>A, c.3334C>T, and a group of at least six of the mutations c.315G>A; c.1498A>G; c.1660C>T; c.3430C>T; c.3528A>G; c.4144C>T; c.4248C>T; and c.6228C>T. These mutated genomes encode one or more mutations selected from R1637H in the 186 kDa readthrough replication protein, A1092V in the 129 kDa replication protein and/or the 186 kDa readthrough replication protein, and at least six mutations selected from G86S, E480G, S534F, A1124V, N1157D, P1362L, P1397S in the 129 kDa replication protein and/or the 186 kDa readthrough replication protein, and the A156V mutation in the coat protein.

An attenuated strain of cucumber green mottle mosaic virus (CGMMV) is useful to protect cucumber plants from infection with the wild-type infectious CGMMV strain. The genome of the attenuated virus contains at least one mutation or group of mutations selected from c.4969G>A, c.3334C>T, and a group of at least six of the mutations c.315G>A; c.1498A>G; c.1660C>T; c.3430C>T; c.3528A>G; c.4144C>T; c.4248C>T; and c.6228C>T. These mutated genomes encode one or more mutations selected from R1637H in the 186 kDa readthrough replication protein, A1092V in the 129 kDa replication protein and/or the 186 kDa readthrough replication protein, and at least six mutations selected from G86S, E480G, S534F, A1124V, N1157D, P1362L, P1397S in the 129 kDa replication protein and/or the 186 kDa readthrough replication protein, and the A156V mutation in the coat protein.

A composition for treating a lysogenic virus, including a vector encoding isolated nucleic acid encoding two or more gene editors chosen from gene editors that target viral DNA, gene editors that target viral RNA, and combinations thereof. A composition for treating a lytic virus, including a vector encoding isolated nucleic acid encoding at least one gene editor that targets viral DNA and a viral RNA targeting composition. A composition for treating both lysogenic and lytic viruses, including a vector encoding isolated nucleic acid encoding two or more gene editors that target viral RNA. A composition for treating lytic viruses. Methods of treating a lysogenic virus or a lytic virus, by administering the above compositions to an individual having a virus and inactivating the virus.