Genetic and antigenic analyses of enterovirus 71 isolates in Taiwan during 1998–2005

Abstract

Enterovirus 71 (EV71) infections can lead to devastating clinical outcomes in children, with an increasing number of severe cases worldwide. The genetic and antigenic variability of EV71 strains isolated in Taiwan in 1998-2005 was evaluated using partial nucleotide sequence analysis of the VP1 gene and the neutralisation assay. Phylogenetic analyses revealed that most EV71 isolates from the 1998 epidemic belonged to sub-genogroup C2, with a minority belonging to sub-genogroup B4. Between 1999 and 2003, isolates belonging to sub-genogroup B4 predominated, followed by a change to sub-genogroup C4 in 2004 and 2005. Antibodies raised in rabbits or collected from infected patients were able to neutralise EV71 virus stocks at high dilutions, regardless of the sub-genogroup of the virus being challenged. The presence of phylogenetically distinct yet antigenically similar populations of EV71 in Taiwan is of concern in the context of herd immunity and vaccine development.

Evolutionary trajectory of the VP1 gene of human enterovirus 71 genogroup B and C viruses

“…Global herd immunity against C1 and C2 viruses possibly explains why epidemics with subgenogroups B4 and C4 are restricted to the Asian Pacific region. This is supported by the results of a Taiwanese study, which showed neutralization of B4 and C4 viruses by C2-specific rabbit antiserum (titres around S. van der Sanden and others 1 : 10 000) (Kung et al, 2007). Subgenogroup B5, however, has recently been described to be antigenically distinct from B1, B4, C2 and C4 viruses (Huang et al, 2009) and could pose a potential risk for epidemic spread outside the Asian region.…”

“…However, these authors do report a slight difference in antigenicity between genogroups A and C and genogroup B (Mizuta et al, 2009). A Taiwanese study showed cross-neutralization of genogroup C viruses by sera of human patients infected with genogroup B (Kung et al, 2007), but this could also be explained by prior exposure rather than cross-neutralization. Our results are in line with another, more recent Taiwanese study, which showed antigenic differences between B1/B4 and C2/C4 on the basis of antigenic cartography, using human serum (Huang et al, 2009).…”

The Association of Recombination Events in the Founding and Emergence of Subgenogroup Evolutionary Lineages of Human Enterovirus 71

“…Screening of large data sets of VP1 sequences provides little if any evidence for any sites in the capsid coding region being subjected to the positive selection that would typically be observed in sites under strong immunological pressure. Consistent with these analyses, there is little evidence from serological cross-neutralization experiments for genogroup-or subgenogroup-specific antibodies, nor indeed the existence of measurable antigenic diversity between EV71 isolates (24,26,28,40,63). However, infections with GgB variants induce higher levels of neutralizing antibodies than GgC, supporting an idea that the emergence of GgC may have been assisted by its intrinsically lower immunogenicity than GgB (40).…”

“…EV71 has been classified into a total of three genogroups (Ggs), designated GgA to GgC (6), showing approximately 13 to 20% amino acid sequence divergence from each other in the VP1 region (6,28) and estimated to have originated from a common ancestor as recently as 1941 (61). Several studies have investigated whether different genogroups or subgenogroups vary in their pathogenicity, which might then explain the variability in outcomes of EV71 infections in different decades and between continents.…”

Reemergence of Enterovirus 71 in 2008 in Taiwan: Dynamics of Genetic and Antigenic Evolution from 1998 to 2008

“…EV71 infection reached epidemic proportions, causing sporadic cases or outbreaks and then becoming prevalent around the AsiaPacific region including Australia, Malaysia, Singapore, Japan, China, and Taiwan for the past 12 years (1, 16-18, 20, 25, 26, 28, 46, 53). Phylogenetic studies have classified EV71 into genotypes A, B, and C, which can be further subdivided into subgentotypes B1 to B5 and C1 to C5 (7,8,17,20,22,25,28,41,45,52,53). These reports indicated that the dominant EV71 strains circulating in the Asia-Pacific region varied genetically, suggesting that the virus was evolving.…”