title: Long-term excretion of vaccine-derived poliovirus by a healthy child.
abstract: A child was found to be excreting type 1 vaccine-derived poliovirus (VDPV) with a 1.1% sequence drift from Sabin type 1 vaccine strain in the VP1 coding region 6 months after he was immunized with oral live polio vaccine. Seventeen type 1 poliovirus isolates were recovered from stools taken from this child during the following 4 months. Contrary to expectation, the child was not deficient in humoral immunity and showed high levels of serum neutralization against poliovirus. Selected virus isolates were characterized in terms of their antigenic properties, virulence in transgenic mice, sensitivity for growth at high temperatures, and differences in nucleotide sequence from the Sabin type 1 strain. The VDPV isolates showed mutations at key nucleotide positions that correlated with the observed reversion to biological properties typical of wild polioviruses. A number of capsid mutations mapped at known antigenic sites leading to changes in the viral antigenic structure. Estimates of sequence evolution based on the accumulation of nucleotide changes in the VP1 coding region detected a "defective" molecular clock running at an apparent faster speed of 2.05% nucleotide changes per year versus 1% shown in previous studies. Remarkably, when compared to several type 1 VDPV strains of different origins, isolates from this child showed a much higher proportion of nonsynonymous versus synonymous nucleotide changes in the capsid coding region. This anomaly could explain the high VP1 sequence drift found and the ability of these virus strains to replicate in the gut for a longer period than expected.
authors.affiliation: Division of Virology, National Institute for Biological Standards and Control, Blanche Lane, Potters Bar, Hertfordshire EN6 3QG, United Kingdom. jmartin@nibsc.ac.uk.
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
authors.forename: Kofi
authors.initials: K
authors.lastname: Odoom
authors.forename: Gráinne
authors.initials: G
authors.lastname: Tuite
authors.forename: Glynis
authors.initials: G
authors.lastname: Dunn
authors.forename: Nicola
authors.initials: N
authors.lastname: Hopewell
authors.forename: Gill
authors.initials: G
authors.lastname: Cooper
authors.forename: Catherine
authors.initials: C
authors.lastname: Fitzharris
authors.forename: Karina
authors.initials: K
authors.lastname: Butler
authors.forename: William W
authors.initials: WW
authors.lastname: Hall
authors.forename: Philip D
authors.initials: PD
authors.lastname: Minor
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D019143:Evolution, Molecular; D005243:Feces / Q000821:virology*; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009154:Mutation; D011051:Poliomyelitis / Q000503:physiopathology / Q000517:prevention & control / Q000821:virology; D017955:Poliovirus / Q000145:classification / Q000276:immunology / Q000302:isolation & purification* / Q000472:pathogenicity; D011055:Poliovirus Vaccine, Oral / Q000008:administration & dosage*; D017422:Sequence Analysis, DNA; D013997:Time Factors; D014611:Vaccination; D017201:Virus Shedding
chemical_list: D000956:Antigens, Viral; D036022:Capsid Proteins; D011055:Poliovirus Vaccine, Oral; C442540:VP1 protein, Poliovirus