Coronaviruses

摘要: In order to survive and propagate, RNA viruses must achieve a balance between the capacity for adaptation new environmental conditions or host cells with need maintain an intact replication competent genome. Several virus families in Nidovirales, such as coronaviruses (CoVs) these objectives largest most complex replicating genomes known, up 32 kb of positive-sense RNA. The CoVs encode sixteen nonstructural proteins (nsp 1-16) known predicted synthesis modification activities, it has been proposed that they are also responsible evolution large genomes. CoVs, including murine hepatitis (MHV) SARS-CoV, 3'-to-5' exoribonuclease activity (ExoN) nsp14. Genetic inactivation ExoN engineered SARS-CoV MHV by alanine substitution at conserved DE-D-D active site residues results viable mutants demonstrate 15- 20-fold increases mutation rates, 18 times greater than those tolerated fidelity other viruses. Thus nsp14-ExoN is essential fidelity, likely serves either direct mediator regulator more proofreading machine, process previously unprecedented biology. Elucidation mechanisms nsp14-mediated will have major implications our understanding viruses, provide robust model investigate diversity pathogenesis. discovery protein distinct from viral RdRp regulates raises possibility genome may be adaptable differing environments selective pressures, rather being fixed determinant.