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Journal of Virology, October 2005, p. 12623-12634, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12623-12634.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Intratypic Recombination among Lineages of Type 1 Vaccine-Derived Poliovirus Emerging during Chronic Infection of an Immunodeficient Patient

Chen-Fu Yang,1 Hour-Young Chen,2 Jaume Jorba,1 Hui-Chih Sun,2 Su-Ju Yang,1 Hsiang-Chi Lee,2 Yhu-Chering Huang,3 Tzou-Yien Lin,3 Pei-Jer Chen,4 Hiroyuki Shimizu,5 Yorihiro Nishimura,5 Andi Utama,5,{dagger} Mark Pallansch,1 Tatsuo Miyamura,5 Olen Kew,1 and Jyh-Yuan Yang2*

Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333,1 Division of Research and Diagnostics, Center for Disease Control, Taipei, Taiwan 115,2 Division of Pediatric Infectious Diseases, Chang Gung Children's Hospital, Taoyuan, Taiwan,3 Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan 110,4 Department of Virology II, National Institute of Infectious Diseases, Tokyo 208-0011, Japan5

Received 27 April 2005/ Accepted 20 July 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.


* Corresponding author. Mailing address: 161 Kun Yang Street, Nan-Kang District, Taipei, Taiwan 115. Phone: 886-2-2653-1375. Fax: 886-2-2653-0403. E-mail: jyyang{at}cdc.gov.tw.

{dagger} Present address: Research Center for Biotechnology, Bogor, Indonesia.


Journal of Virology, October 2005, p. 12623-12634, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12623-12634.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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Copyright © 2005 by the American Society for Microbiology. All rights reserved.