Molecular evolution and antigenic drift of type 3 iVDPVs excreted from a patient with immunodeficiency in Ningxia, China

J Med Virol. 2023 Jan;95(1):e28215. doi: 10.1002/jmv.28215. Epub 2022 Oct 19.

Abstract

A 2.5-year-old pediatric patient with acute flaccid paralysis was diagnosed with primary immunodeficiency (PID) in Ningxia Province, China, in 2011. Twelve consecutive stool specimens were collected from the patient over a period of 10 months (18 February 2011 to 20 November 2011), and 12 immunodeficiency vaccine-derived poliovirus (iVDPV) strains (CHN15017-1 to CHN15017-12) were subsequently isolated. Nucleotide sequencing analysis of the plaque-purified iVDPVs revealed 2%-3.5% VP1-region differences from their parental Sabin 3 strain. Full-length genome sequencing showed they were all Sabin 3/Sabin 1 recombinants, sharing a common 2C-region crossover site, and the two key determinants of attenuation (U472C in the 5' untranslated region and T2493C in the VP1 region) had reverted. Temperature-sensitive experiments demonstrated that the first two iVDPV strains partially retained the temperature-sensitive phenotype's nature, while the subsequent ten iVDPV strains distinctly lost it, possibly associated with increased neurovirulence. Nineteen amino-acid substitutions were detected between 12 iVDPVs and the parental Sabin strain, of which only one (K1419R) was found on the subsequent 10 iVDPV isolates, suggesting this site's potential as a temperature-sensitive determination site. A Bayesian Monte Carlo Markov Chain phylogenetic analysis based on the P1 coding region yielded a mean iVDPV evolutionary rate of 1.02 × 10-2 total substitutions/site/year, and the initial oral-polio-vaccine dose was presumably administered around June 2009. Our findings provide valuable information regarding the genetic structure, high-temperature growth sensitivity, and antigenic properties of iVDPVs following long-term evolution in a single PID patient, thus augmenting the currently limited knowledge regarding the dynamic changes and evolutionary pathway of iVDPV populations with PID during long-term global replication.

Keywords: antigenic drift; molecular evolution; type 3 immunodeficiency vaccine-derived poliovirus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigenic Drift and Shift
  • Bayes Theorem
  • Evolution, Molecular
  • Humans
  • Immunologic Deficiency Syndromes* / complications
  • Phylogeny
  • Poliomyelitis* / prevention & control
  • Poliovirus Vaccine, Oral
  • Poliovirus*

Substances

  • Poliovirus Vaccine, Oral