We characterized the genetic diversity of the complete VP1 region of coxsackievirus A16 (CA16) and enterovirus 71 (EV71) isolated from patients with hand, foot, and mouth disease in Toyama from 1981 to 2007 to evaluate the relationship between epidemics and genetic changes. The predominant genogroups of CA16 changed from B to C in 1995-1998, and genogroup C further changed from subgenogroup C1 to C2 around 2002, and to C3 in 2005-2007. The subgenogroups of the EV71 isolates were classified into B1, B4, C1, and C3 in 1983-1994, and into C4 in 1997-2006. However, changes of the amino acid sequences of the VP1 regions of CA16 were restored, and those of the EV71 isolates were not observed among the same subgenogroups during this survey period, indicating that the prevalence that occurred at intervals of several years seemed to depend on an accumulating number of immunologically naive children, not viral antigenic changes.
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