Genetic characterization and molecular evolution of type 3 vaccine-derived polioviruses from an immunodeficient patient in China.

• These type 3 iVDPVs evolved very rapidly after infection of humans, showing a mean substitution rate of 1.76 × 10−2 substitutions/site/year. • Continuous evolution over time is an important feature of iVDPVs. • Multiple variants and lineages have been diverged for rapid adaptation to new environments and resistance to host immune stress. • All iVDPVs were vaccine recombinants, and partial genome exchange may have an impact on the virulence. • The VP2-162 amino acid may be a novel key site affecting the temperature sensitivity phenotype. 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. [ABSTRACT FROM AUTHOR]