Common and Diverse Features of Cocirculating Type 2 and 3 Recombinant Vaccine-Derived Polioviruses Isolated From Patients With Poliomyelitis and Healthy Children

J Infect Dis. 2012 May 1;205(9):1363-73. doi: 10.1093/infdis/jis204. Epub 2012 Mar 29.

Abstract

Background: Five cases of poliomyelitis due to type 2 or 3 recombinant vaccine-derived polioviruses (VDPVs) were reported in the Toliara province of Madagascar in 2005.

Methods: We sequenced the genome of the VDPVs isolated from the patients and from 12 healthy children and characterized phenotypic aspects, including pathogenicity, in mice transgenic for the poliovirus receptor.

Results: We identified 6 highly complex mosaic recombinant lineages composed of sequences derived from different vaccine polioviruses and other species C human enteroviruses (HEV-Cs). Most had some recombinant genome features in common and contained nucleotide sequences closely related to certain cocirculating coxsackie A virus isolates. However, they differed in terms of their recombinant characteristics or nucleotide substitutions and phenotypic features. All VDPVs were neurovirulent in mice.

Conclusions: This study confirms the genetic relationship between type 2 and 3 VDPVs, indicating that both types can be involved in a single outbreak of disease. Our results highlight the various ways in which a vaccine-derived poliovirus may become pathogenic in complex viral ecosystems, through frequent recombination events and mutations. Intertypic recombination between cocirculating HEV-Cs (including polioviruses) appears to be a common mechanism of genetic plasticity underlying transverse genetic variability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Child
  • Disease Outbreaks*
  • Enterovirus C, Human / immunology
  • Enterovirus C, Human / pathogenicity
  • Female
  • Genome, Viral*
  • Humans
  • Madagascar / epidemiology
  • Male
  • Mice
  • Phenotype
  • Phylogeny
  • Poliomyelitis / epidemiology*
  • Poliomyelitis / immunology
  • Poliomyelitis / prevention & control
  • Poliovirus / genetics
  • Poliovirus / isolation & purification*
  • Poliovirus / pathogenicity
  • Poliovirus Vaccines / adverse effects
  • Protein Conformation
  • RNA, Viral / genetics*
  • Recombination, Genetic
  • Sequence Analysis, DNA
  • Vaccines, Synthetic / adverse effects

Substances

  • Poliovirus Vaccines
  • RNA, Viral
  • Vaccines, Synthetic