A single amino acid mutation in VP1 of coxsackievirus A6 determining efficiency of VP0 cleavage and proliferation

CV-A6 is a major pathogen in the context of HFMD. The cost of treatment and hospitalization of children with HFMD may have a considerable financial impact on the families of patients. CV-A6 is a member of picornaviruses and forms infectious virion through maturation cleavage of VP0 into VP4 and VP2. Although it is well accepted that the autocatalytic process involves viral RNA, the detailed mechanism remains unclear. In this study, residues in VP1-143 were demonstrated to regulate the efficiency of VP0 cleavage and affect the ratio of provirion and virion. Glycine-to-arginine mutation was tolerant, not abolished, but affected the efficiency of VP0 cleavage. The results support a theory that residue mutations on a structural protein of a serotype/genotype within enteroviruses, not well-conserved across picornaviruses and far away from the VP0 cleavage site on the outside surface, regulate the efficiency of VP0 cleavage and render phenotypically different strains.