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Coronaviruses encode a proofreading exoribonuclease that is responsible for genome expansion, increased robustness to mutations, and resistance to mis-incorporations during RNA synthesis, as well as being required for virulence. The stability of the ExoN− genotype and phenotype provides a powerful model for the study of additional CoV fidelity determinants and of the effects of altered fidelity on virus replication, fitness, host-species range, and response to environmental changes. Experiments testing the proposed multi-subunit fidelity complex will yield exciting new insights into how CoVs ignore the RNA virus playbook and instead seem to play by their own rules while dancing on the edge of genetic disaster.

Coronaviruses as DNA Wannabes: A New Model for the Regulation of RNA Virus Replication Fidelity