Yang Chen-Fu, Chen Hour-Young, Jorba Jaume, Sun Hui-Chih, Yang Su-Ju, Lee Hsiang-Chi, Huang Yhu-Chering, Lin Tzou-Yien, Chen Pei-Jer, Shimizu Hiroyuki, Nishimura Yorihiro, Utama Andi, Pallansch Mark, Miyamura Tatsuo, Kew Olen, Yang Jyh-Yuan
Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
J Virol. 2005 Oct;79(20):12623-34. doi: 10.1128/JVI.79.20.12623-12634.2005.
We determined the complete genomic sequences of nine type 1 immunodeficient vaccine-derived poliovirus (iVDPV) isolates obtained over a 337-day period from a poliomyelitis patient from Taiwan with common variable immunodeficiency. The iVDPV isolates differed from the Sabin type 1 oral poliovirus vaccine (OPV) strain at 1.84% to 3.15% of total open reading frame positions and had diverged into at least five distinct lineages. Phylogenetic analysis suggested that the chronic infection was initiated by the fifth and last OPV dose, given 567 days before onset of paralysis, and that divergence of major lineages began very early in the chronic infection. Key determinants of attenuation in Sabin 1 had reverted in the iVDPV isolates, and representative isolates of each lineage showed increased neurovirulence for PVR-Tg21 transgenic mice. None of the isolates had retained the temperature-sensitive phenotype of Sabin 1. All isolates were antigenic variants of Sabin 1, having multiple amino acid substitutions within or near neutralizing antigenic sites 1, 2, and 3a. Antigenic divergence of the iVDPV variants from Sabin 1 followed two major independent evolutionary pathways. The emergence of distinct coreplicating lineages suggests that iVDPVs can replicate for many months at separate sites in the gastrointestinal tract. Some isolates had mosaic genome structures indicative of recombination across and within lineages. iVDPV excretion apparently ceased after 30 to 35 months of chronic infection. The appearance of a chronic VDPV excretor in a tropical, developing country has important implications for the strategy to stop OPV immunization after eradication of wild polioviruses.
我们测定了从一名患有常见可变免疫缺陷的台湾脊髓灰质炎患者身上，在337天内分离得到的9株1型免疫缺陷疫苗衍生脊髓灰质炎病毒（iVDPV）的完整基因组序列。这些iVDPV分离株与Sabin 1型口服脊髓灰质炎疫苗（OPV）株相比，在总开放阅读框位置的1.84%至3.15%处存在差异，并已分化为至少五个不同的谱系。系统发育分析表明，慢性感染是由在麻痹发作前567天给予的第五剂也是最后一剂OPV引发的，并且主要谱系的分化在慢性感染早期就已开始。Sabin 1株中减毒的关键决定因素在iVDPV分离株中发生了逆转，每个谱系的代表性分离株对PVR-Tg21转基因小鼠的神经毒力增强。所有分离株均未保留Sabin 1的温度敏感表型。所有分离株都是Sabin 1的抗原变体，在中和抗原位点1、2和3a内或附近有多个氨基酸替换。iVDPV变体与Sabin 1的抗原分化遵循两条主要的独立进化途径。不同共复制谱系的出现表明iVDPV可以在胃肠道的不同部位复制数月。一些分离株具有镶嵌基因组结构，表明在谱系间和谱系内发生了重组。慢性感染30至35个月后，iVDPV排泄显然停止。在一个热带发展中国家出现慢性VDPV排泄者，对于在根除野生脊髓灰质炎病毒后停止OPV免疫的策略具有重要意义。
