Intratypic recombination among lineages of type 1 vaccine-derived poliovirus emerging during chronic infection of an immunodeficient patient

Chen Fu Yang, Hour Young Chen, Jaume Jorba, Hui Chih Sun, Su Ju Yang, Hsiang Chi Lee, Yhu Chering Huang, Tzou Yien Lin, Pei Jer Chen, Hiroyuki Shimizu, Yorihiro Nishimura, Andi Utama, Mark Pallansch, Tatsuo Miyamura, Olen Kew, Jyh Yuan Yang

研究成果: 雜誌貢獻文章同行評審

69 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)12623-12634
頁數12
期刊Journal of Virology
79
發行號20
DOIs
出版狀態已發佈 - 2005
對外發佈

ASJC Scopus subject areas

  • 免疫學
  • 病毒學

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