期刊
JOURNAL OF INFECTIOUS DISEASES
卷 205, 期 9, 页码 1363-1373出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jis204
关键词
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资金
- Transverse Research Program [PTR-276]
- Agence Nationale pour la Recherche
- Agence Inter-etablissements de Recherche pour le Developpement [ANR 09 MIEN 019]
- Fondation pour la Recherche Medicale (FRM) [DMI20091117313]
- French Institut de Veille Sanitaire (InVS)
- Fondation Merieux
- Rotary International
- Region Ile-de-France
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.
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