Evolution of the Sabin Strain of Type 3 Poliovirus in an Immunodeficient Patient during the Entire 637-Day Period of Virus Excretion

Abstract

A 20-year-old female hypogammaglobulinemic patient received monotypic Sabin 3 vaccine in 1962. The patient excreted type 3 poliovirus for a period of 637 days without developing any symptoms of poliomyelitis, after which excretion appeared to have ceased spontaneously. The evolution of Sabin 3 throughout the entire period of virus excretion was studied by characterization of seven sequential isolates from the patient. The isolates were analyzed in terms of their antigenic properties, virulence, sensitivity for growth at high temperatures, and differences in nucleotide sequence from the Sabin type 3 vaccine. The isolates followed a main lineage of evolution with a rate of nucleotide substitution that was very similar to that estimated for wild-type poliovirus during person-to-person transmission. There was a delay in the appearance of antigenic variants compared to sequential type 3 isolates from healthy vaccines, which could be one of the possible explanations for the long-term excretion of virus from the patient. The distribution of mutations in the isolates identified regions of the virus possibly involved in adaptation for growth in the human gut and virus persistence. None of the isolates showed a full reversion of the attenuated and temperature-sensitive phenotypes of Sabin 3. Information of this sort will help in the assessment of the risk of spread of virulent polioviruses from long-term excretors and in the design of therapies to stop long-term excretion. This will make an important contribution to the decision-making process on when to stop vaccination once wild poliovirus has been eradicated.

Comparison of poliovirus recombinants: accumulation of point mutations provides further advantages

“…There were no changes in the antigenic sites or the CRE region of 557TAG 668GAA VP4 759AAG 759AAG 759AAG 820CAT 961GAA 865GAA VP2 1233TAC 1233TAC 1233TAC 1040TAA 100SAT 1117AAG 1371CAT 1120TAC 1222GAA 1258AAG 1463GAA 241EAK 1645CAT VP3 1990AG 415TAAD 1861TAC 1873AAG 2250GAA 2084AAG 448TAA 1991GAA 2409GAA 2409GAA 2410CAT 2150AAG 470IAV 2413TAC 2431AAG 2419TAA 559DAE VP1 2526AAG 2834TAC 2637CAT 632AAV 2909TAC 721IATd 2909TAC 721IATd 3367GAA 2790TAC 683MAT 2932TAC 3084TAA 3084TAA 3084TAA 3330TAA 3378GAA 2A 3455AAT 903QAL 3460AAG 3364TAC 3658AAG 3409TAA 3682CAT 3511AAT 923KAN 3552CAT 937AAV 2B 4029CAT 3945AAG 4071GAA 2C 4308CAA 4129GAA 1395DAN 4188GAA 4473GAA § 4473GAA § 4473GAA § 4925GAA 4299TAC 4779AAG 4779AAG 4443TAC 4893CAT 4800TAC 5011TAA 1422SAT 5091CAT 3A 5341GAA 5119CAT 5342TAC 1532VAT 3B 5343CAT 1600IAV 3C 5514GAA 5449CAT 5545AAG 5562AAG 5536CAT 5845CAT 5595GAA 5800AAG 5884TAC 5925TAC 5833TAC 5932CAT 5972CAA 1745TAN 3D 6183GAA 6183GAA 6183GAA 6205CAT 6078TAC either of the PV3 strains. In contrast, there were several other nucleotide changes in both PV3 recombinants; however, these were not in the same sites as in other reported PV3 OPV-derived strains (Martin et al, 2000).…”

Molecular Analysis of Enteroviruses

“…High RNA virus error rates are necessary to enable survival of the virus population under selective pressure [106]. The molecular diversity and evolution of EVs occurs through genetic drift and, over much longer periods, antigenic diversification in the structural gene region encoding the virus capsid, including VP1 [61,107]. Sequence changes occur rapidly in the capsid region [61].…”

Plaque And Growth Characteristics Of Different Polioviruses Isolated From Acute Flaccid Paralysis In Northern Nigeria

“…Poliovirus is among the most rapidly evolving viruses known, with about one percent nucleotide substitution per site per year (4). Therefore, OPV recipients usually excrete altered vaccine viruses after vaccination (3).…”