Erasmus Medical Center, Department of Virology, Rotterdam, The Netherlands.
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
J Gen Virol. 2010 Aug;91(Pt 8):1949-1958. doi: 10.1099/vir.0.019695-0. Epub 2010 Apr 7.
From 1963 to 1986, human enterovirus 71 (HEV71) infections in the Netherlands were successively caused by viruses of subgenogroups B0, B1 and B2. A genogroup shift occurred in 1987, after which viruses of subgenogroups C1 and C2 were detected exclusively. This is in line with HEV71 typing in Australia, Europe and the USA, but is distinct from that in the Asian Pacific region, where HEV71 subgenogroups B3-B5 and C4-C5 have caused large outbreaks since 1997. To understand these observations in HEV71 epidemiology, the VP1-encoding regions of 199 HEV71 strains isolated in the Netherlands between 1963 and 2008 were used to study the detailed evolutionary trajectory and population dynamics of HEV71. Genogroup B viruses showed an epochal evolution, whereas genogroup C viruses evolved independently, which is in line with the co-circulation of C1 and C2 viruses in the Netherlands since 1997. Considering that strains from the Netherlands are interspersed phylogenetically with GenBank reference strains, the evolution of B1-B2, C1-C2 viruses has a global nature. Phylodynamic analysis confirmed that increased reporting of HEV71 infections in 1986 and 2007 reflected true epidemics of B2 and C2 viruses, respectively. Sequence analysis of the complete capsid region of a subset of isolates revealed several (sub)genogroup-specific residues. Subgenogroup B2-specific rabbit antiserum showed cross-neutralization of B0, B1 and B2 viruses, but not of subgenogroup C1 or C2 viruses, probably explaining the global shift to genogroup C in 1987 following a B2 epidemic. Anti-C1 rabbit serum neutralized both 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.
从 1963 年到 1986 年，荷兰的人类肠道病毒 71 型（HEV71）感染相继由亚基因组 B0、B1 和 B2 的病毒引起。1987 年发生了基因亚组转变，此后仅检测到亚基因组 C1 和 C2 的病毒。这与澳大利亚、欧洲和美国的 HEV71 分型一致，但与亚太地区不同，自 1997 年以来，HEV71 亚基因组 B3-B5 和 C4-C5 已导致大规模爆发。为了了解 HEV71 流行病学中的这些观察结果，使用在 1963 年至 2008 年间在荷兰分离的 199 株 HEV71 毒株的 VP1 编码区来研究 HEV71 的详细进化轨迹和种群动态。B 组病毒显示出阶段性进化，而 C 组病毒则独立进化，这与 1997 年以来荷兰 C1 和 C2 病毒的共同循环一致。考虑到来自荷兰的菌株在系统发育上与 GenBank 参考菌株交织在一起，B1-B2、C1-C2 病毒的进化具有全球性。系统发育动力学分析证实，1986 年和 2007 年 HEV71 感染报告的增加反映了 B2 和 C2 病毒的真正流行。一组分离株的完整衣壳区序列分析揭示了几个（亚）基因组特异性残基。B2 亚基因组特异性兔抗血清显示对 B0、B1 和 B2 病毒的交叉中和，但对 C1 或 C2 病毒没有中和作用，这可能解释了 1987 年 B2 流行后全球向 C 组的转变。抗 C1 兔血清中和了 B 和 C 组病毒。针对 C1 和 C2 病毒的全球群体免疫力可能解释了为什么 B4 和 C4 亚组的流行局限于亚太地区。
