Collective behavior of viruses was documented with mutant RNA viruses resistant to nucleotide analogues. The study of this class of mutants has been instrumental for the understanding of the molecular basis of template copying fidelity, and the consequences of fidelity alterations in the adaptive capacity and pathogenic potential of RNA viruses. In the first mutant studied, amino acid substitution G46S in the PV polymerase resulted in about four-fold increase in template-copying fidelity. This modification reduced PV adaptability and infective potential in vivo. The mutant in isolation did not replicate efficiently in the brain of susceptible mice, but it did when its mutant spectrum was broadened by 5-fluorouracil mutagenesis or when it was co-inoculated with wild type PV.