IMMUNODEFICIENCY-ASSOCIATED VDPV TYPE 2 CASE FROM ARGENTINA IN 2016

LEMA C; TORRES C; PASINOVICH M; BULLARD K; SCHMIDT A; CASTRO C; BURNS C; FREIRE MC; JORBA J

Conferencia; Virus Genomics and Evolution 2021, Wellcome Connecting Science; 2021

We studied the intra-patient evolution of eleven type 2 immunodeficient vaccine-derived poliovirus(iVDPV2) isolates and eight Echovirus 3 (E3) isolates obtained over a 352-day and 124-day periodrespectively during 2016. The patient was vaccinated with two doses of trivalent oral poliovirusvaccine (tOPV), but did not present paralysis. Add he had X-Linked agammaglobulinemia and he was from Argentina. The similarity of the iVDPV isolates from the Sabin type 2 OPV strain ranged from 99.49% to 99.59% of total open reading frame (ORF) positions and phylogenetic analysis suggested the detection of one evolutionary lineage. Nucleotide substitutions along the genome were mostly uniformly distributed among the distinct genome regions, particularly in the non-structural regions.Eighty-five nucleotide and 12 amino acid changes were inferred throughout the genome. Phylodynamics analysis of the eleven iVDPV2 isolates were consistent with stepwise accumulation of substitutions from the Sabin 2 originating dose. The substitution rates estimated from five different regions (ORF, P1, P2, P3 and VP1) following different clocks models ranged between 9.46 × 10-3 and 1.65 × 10-2 substitutions/site/year. In addition, molecular clock analysis suggested that the infection was initiated by the first tOPV dose given in November 2015; the mean value and the distribution of date estimates were consistently earlier to the date of the second tOPV dose (February 2016) and were compatible with the date of the first tOPV dose. All estimated dates were prior to the scheduled tOPV to bOPV switch date in Argentina (April 2016). The two key determinants of attenuation in Sabin 2 had reverted in the Sabin and iVDPV isolates. No amino acid changes in antigenic sites or hypervariable region of VP1 were observed for any of the 11 samples. iVDPV excretion apparently ceased after first day treatment whit the antiviral pocapavir. The substitution rate for Echovirus 3 isolates was estimated as 1.73 × 10-2 s/s/y and would have started its diversification in December 2016. The substitution rates estimated here for VDPV2 are agree with those described for VDPV and polioviruses. The intra-patient substitution rate for E3 is estimated here for the first time and in this case, it is similar to that of PV2. Understanding intra-patient evolution of persistent iVDPV infections is important for assessing the risk of iVDPV spread and it is critical for achieving and maintaining the goal of polio eradication.