Evolution of EV71 genogroup in Taiwan from 1998 to 2005: An emerging of subgenogroup C4 of EV71

Abstract

In Taiwan, enterovirus 71 (EV71) has played an important role in severe enterovirus-related cases every year since the devastating outbreak in 1998. Three genogroups A, B, C occur worldwide; with the B and C genogroups being subdivided into B1-B4 and C1-C4 subgenogroups respectively. To understand the mutation of the EV71 genogroup in Taiwan before and after 1998, a total of 54 worldwide strains were studied including 41 Taiwanese strains obtained in 1986 and 1998-2004. A fragment of 207 bp of the VP4 region was amplified and sequenced. Genetic analysis was performed using MEGA software (version 3.0) for the nucleotide sequence alignment and phylogenetic analysis. In Taiwan, the subgenogroup B1 was predominant before 1998 while subgenogroup C2 was the major etiologic group in 1998 outbreak. A minor etiologic group outbreak in 1998, subgenogroup B4, became predominant during the period from 1999 to 2003. In this study, subgenogroup C4 emerged and became predominant in 2004 in Taiwan. The nucleotide differences between B1 and C2, C2 and B4, B4 and C4 were 20%-26%, 19%-27%, 18%-22%, respectively. Nucleotide sequence alignment revealed 67 substitutions. Most of the substitutions (62/67) were silent mutations. This is the first report about the emergence of EV71 subgenogroup C4 in Taiwan.

Evolutionary Genetics of Human Enterovirus 71: Origin, Population Dynamics, Natural Selection, and Seasonal Periodicity of the VP1 Gene

“…Developing an EV-71 vaccine may present a daunting challenge if actively circulating subgenogroups are antigenically distinct. Multiple EV-71 subgenogroups can cocirculate during an outbreak (1,46,82), and rapid switching among subgenogroups has become increasingly common, perhaps caused by virus importation, evolution of novel lineages, or other factors (14,39,48,57,82). Although broadly neutralizing antibodies against selected EV-71 subgenogroups have been reported in animal models (6,27,49,54,83), the degree of cross-protection and the potential for EV-71 escape evolution in humans remain uninvestigated and unknown.…”

An Attenuated Strain of Enterovirus 71 Belonging to Genotype A Showed a Broad Spectrum of Antigenicity with Attenuated Neurovirulence in Cynomolgus Monkeys

“…There have also been reports of antigenic heterogeneity among EV71 isolates, including a maximum difference in neutralization titers of 32-fold between different rabbit sera after EV71 inoculation (19). Frequent changes in the genotype of circulating EV71 may in part reflect antigenic variation in cross-neutralization between genotypes that may be critical for the perpetuation of EV71 (27,37,41,55).…”

“…Isolates from the outbreak in Bulgaria in 1975 and the outbreak in Hungary in 1978 belong to genotype B1. In more recent EV71 outbreaks in Asia, genotype C4 was predominant (26,27,37). These findings indicate that, in general, the genotype is not the sole determinant of the observed pathogenesis of EV71 (14,50).…”

“…RD cells were used for preparation of stocks of other virus strains, titration of those viruses, and neutralization assays. The following EV71 strains were used: EV71(BrCr-TR), a genotype A temperatureresistant variant of the prototype BrCr strain; EV71(S1-3Ј), a genotype A temperature-sensitive mutant of the prototype BrCr strain; Nagoya (genotype B1) (16) (26,27,37). In cynomolgus monkeys, EV71(BrCr-TR) has the neurovirulent phenotype of the BrCr strain and EV71(S1-3Ј) has an attenuated phenotype (5,17,39,40).…”

Study on the Clinical Characteristics of Hand-Foot-Mouth Disease Caused by Enterovirus 71 and Other Enteroviruses

“…The results of the study suggest that the disease in children infected with EV71 is more severe than that in children with CoxA16, and the incidence is less noticeable. As a result, both the duration of illness and the heat increase significantly [6]. CoxA16 disease is more easily noticeable, timely detection and timely diagnosis and treatment, this may also be an important reason for the low viral load of CoxA16.…”