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Published on: March 8, 2012
Genetic characterization and molecular evolution of type 3 vaccine-derived polioviruses from an immunodeficient
Qin Guo1, Shuangli Zhu2, Dongyan Wang2
1National Polio Laboratory, WHO WPRO Regional Polio Reference Laboratory, National Health Commission Key Laboratory for Biosecurity, National Health Commission Key Laboratory for Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention Beijing, China; Da Zhou Vocational College of Chinese Medicine, Dazhou, China.
Abstract:
In 2013, a case of immunodeficiency vaccine-derived poliovirus (iVDPV) was identified in Jiangxi Province, China. In this study, we purified 14 type 3 original viral isolates from this case and characterized the molecular evolution of these iVDPVs for 298 days. Genetic variants were found in most of the original viral isolates, with complex genetic and evolutionary relationships among the variants. A phylogenetic tree constructed based on the P1 region showed that these iVDPVs were classified into lineage A and B. The dominant lineage B represents a major trend in virus evolution. The nucleotide substitution rate at the third codon position (3CP) estimated by the BEAST program was 1.76 × 10-2 substitutions/site/year (95% HPD: 1.23-2.39 × 10-2). The initial OPV dose was given dating back to March 2013, which was close to the time of the last OPV vaccination, suggesting that OPV infection may have originated with the last dose of vaccine. Recombinant analysis showed that these iVDPVs were inter-vaccine recombinants with two recombination patterns, S3/S2/S1 and S3/S2/S3/S2/S1. Whole genome sequence analysis revealed that key nucleotide sites (C472U, C2034U, U2493C) associated with the attenuated phenotype of Sabin 3 have been replaced. Temperature sensitivity test showed that all tested strains were temperature-sensitive, except for the variant Day11-5. Interestingly, we observed that the variant Day11-5 temperature resistance properties may be associated with the Lys to Met substitution at the VP2-162 site. Serological test and whole genome sequence analysis showed that the seropositivity rate remained high, and mutations in the antigenic sites did not significantly alter neutralization ability.
Insights
A 2013 Chinese case of immunodeficiency vaccine-derived poliovirus (iVDPV) showed complex evolution over 298 days. The dominant lineage B and recombinant patterns suggest OPV infection originated from the last vaccine dose.
Area of Science:
- Virology
- Molecular Evolution
- Vaccine-Derived Pathogens
Background:
- A 2013 case of immunodeficiency vaccine-derived poliovirus (iVDPV) type 3 was identified in Jiangxi Province, China.
- This study investigated the molecular evolution of 14 iVDPV isolates over 298 days.
Observation:
- Phylogenetic analysis revealed two lineages (A and B), with lineage B dominating virus evolution.
- The estimated nucleotide substitution rate at the third codon position (3CP) was 1.76 × 10⁻² substitutions/site/year.
- Recombinant analysis identified two patterns: S3/S2/S1 and S3/S2/S3/S2/S1.
Findings:
- Key Sabin 3 attenuation sites (C472U, C2034U, U2493C) were altered in the iVDPVs.
- Most strains were temperature-sensitive, except for variant Day11-5, potentially due to a VP2-162 Lys to Met substitution.
- High seropositivity rates persisted, with mutations in antigenic sites not significantly affecting neutralization.
Implications:
- The findings suggest OPV infection may have originated from the last vaccine dose.
- Understanding iVDPV evolution is crucial for polio eradication strategies.
- The identified mutations and altered phenotypes provide insights into poliovirus adaptation and virulence.
