The Molecular Evolution of Type 2 Vaccine-Derived Polioviruses in Individuals with Primary Immunodeficiency Diseases

Figures

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  Figure 1. The phylogenetic tree of VP1 sequences in 157 iVDPV2 isolates. The sequence alignment was constructed using Clustal Omega, and the tree was inferred using the FastTree 2.1.10 [48] with the GTR model and gamma distribution and visualized with FigTree. Large genetic clusters of each case study are indicated by different colors, red for a chronic excretor in the United Kingdom 1995–2013 [45], blue for the environmental samples from Slovakia in 2003–2005 [43], and green for the stool and oropharyngeal samples from Israel in 2018 [46,47].

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  Figure 2. The frequency of synonymous and non-synonymous substitutions of the VP1 amino acid sequences from 157 iVDPV2 and 567 cVDPV2 isolates. Sequence divergence was analyzed using SNAP (Synonymous Non-synonymous Analysis Program, https://www.hiv.lanl.gov/content/sequence/SNAP/SNAP.html (accessed on 28 May 2021)) [54]. The synonymous (blue crosses) and non-synonymous substitutions (red circles) of the VDPV sequence relative to the Sabin 2 strain are depicted. (A) iVDPV2. (B) cVDPV2.

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  Figure 3. The number of amino acid substitutions in each position of the P1 capsid region of 19 iVDPV2 isolates. The amino acid substitutions in the neutralizing antigenic (NAg) sites are shown in red. The positions of hypervariable residues (HVRs) at the N-terminal and a gatekeeper substitution at VP1–143 of VP1 are indicated.

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  Figure 4. The locations of amino acid substitutions in selected iVDPV2 isolates. The three-dimensional structure of type 2 wild poliovirus strain MEF-1 was obtained from PDB 1EAH and represented as a pentameric unit ((A): outside; (B): inside of capsid). Each protomer contains a single copy of VP1, VP2, VP3, and VP4 distinguished by gray colors. The location of frequent amino acid substitutions (more than 4 out of 19 iVDPV2 isolates) relative to the Sabin 2 strain is colored. The neutralizing antigenic sites are red. The hypervariable residues and the gatekeeper substitution of VP1-143 are green. Other amino acid changes are blue. The image was generated using PyMOL 2.4.2 (Schrödinger).