Cooperation between different RNA virus genomes produces a new phenotype

An RNA virus population generally evolves rapidly under selection pressure, because of high error rates of the viral RNA polymerase. Measles virus, an enveloped RNA virus, has a fusion protein mediating fusion of the viral envelope with the cell membrane. Here we observe that a non-fusogenic recombinant measles virus evolves, after passages, into mutant viruses which regain the ability to induce membrane fusion. Unexpectedly, we identify a mutant virus possessing two types of genomes within a single virion: one genome encoding the wild-type fusion protein, the other a mutant version with a single amino-acid substitution. Neither the wild-type nor mutant protein by itself is able to mediate membrane fusion, but both together exhibit enhanced fusion activity through hetero-oligomer formation. Our results reveal a molecular mechanism for the ‘cooperation’ between different RNA virus genomes, which may have implications in viral evolution and in the evolution of other macromolecules.