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Molecular evolution and antigenic drift of type 3 iVDPVs excreted from a patient with immunodeficiency in Ningxia,
Qin Fan1,2, Jiangtao Ma3, Xiaolei Li1
1National Laboratory for poliomyelitis, WHO WPRO Regional Polio Reference Laboratory, National Health Commission Key Laboratory for Biosafety and National Health Commission Key Laboratory for Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.
Insights
In a pediatric patient with primary immunodeficiency (PID), 12 vaccine-derived poliovirus strains evolved over 10 months. These strains lost temperature sensitivity, indicating potential neurovirulence and altered evolutionary pathways in PID patients.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Primary immunodeficiency (PID) can lead to prolonged poliovirus shedding.
- Vaccine-derived polioviruses (VDPVs) can evolve in immunocompromised individuals.
- Understanding VDPV evolution in PID is crucial for public health.
Purpose of the Study:
- To characterize the genetic and phenotypic evolution of immunodeficiency vaccine-derived poliovirus (iVDPV) strains.
- To investigate the evolutionary rate and neurovirulence determinants of iVDPVs in a PID patient.
- To enhance knowledge of iVDPV dynamics in immunocompromised individuals.
Main Methods:
- Isolation and sequencing of 12 iVDPV strains from stool specimens.
- Full-length genome sequencing and nucleotide analysis.
- Temperature-sensitive phenotype experiments and phylogenetic analysis.
Main Results:
- Isolated iVDPV strains were Sabin 3/Sabin 1 recombinants with reverted attenuation markers.
- Early strains showed partial temperature sensitivity, while later strains lost it.
- A specific amino acid substitution (K1419R) was associated with loss of temperature sensitivity.
Conclusions:
- iVDPVs in PID patients can undergo significant genetic and phenotypic changes.
- Loss of temperature sensitivity may correlate with increased neurovirulence.
- Long-term iVDPV evolution in PID provides insights into viral adaptation and public health risks.
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.
