Intratypic recombination among lineages of type 1 vaccine-derived poliovirus emerging during chronic infection of an immunodeficient patient.
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.
Yang
Chen-Fu
CF
Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
Chen
Hour-Young
HY
Jorba
Jaume
J
Sun
Hui-Chih
HC
Yang
Su-Ju
SJ
Lee
Hsiang-Chi
HC
Huang
Yhu-Chering
YC
Lin
Tzou-Yien
TY
Chen
Pei-Jer
PJ
Shimizu
Hiroyuki
H
Nishimura
Yorihiro
Y
Utama
Andi
A
Pallansch
Mark
M
Miyamura
Tatsuo
T
Kew
Olen
O
Yang
Jyh-Yuan
JY
D019943:Amino Acid Substitution; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics; D001483:Base Sequence; D002648:Child; D002908:Chronic Disease; D017074:Common Variable Immunodeficiency / Q000150:complications*; D005243:Feces / Q000821:virology; D005260:Female; D016679:Genome, Viral; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010614:Pharynx / Q000821:virology; D010802:Phylogeny; D011051:Poliomyelitis / Q000517:prevention & control* / Q000821:virology*; D017955:Poliovirus / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D011055:Poliovirus Vaccine, Oral / Q000008:administration & dosage*; D011995:Recombination, Genetic; D016415:Sequence Alignment; D014611:Vaccination; D014774:Virulence
D000956:Antigens, Viral; D011055:Poliovirus Vaccine, Oral