Polio eradication, cessation of vaccination and re-emergence of disease

Additional mutations encoding amino acid substitutions in the capsid region contribute to and stabilize the attenuated phenotype of Sabin strains.

“Additional mutations encoding amino acid substitutions in the capsid region contribute to and stabilize the attenuated phenotype.”

Substitutions in the IRES contribute most to the attenuated phenotype of the Sabin 1 and Sabin 3 strains.

“The substitutions in the IRES, which alter stem-loop structures (63, 68, 126, 132) and reduce the efficiency of initiation of translation of the poliovirus RNA template (68, 188), contribute most to the attenuated phenotype of the Sabin 1 and Sabin 3 strains.”

Only three substitutions (C472U in the IRES, C2034U encoding an S → F substitution at position 91 of VP3, and U2493C encoding an I → T substitution at position 6 of VP1) appear to be the main determinants of the attenuated phenotype of Sabin 3.

“Onlythree substitutions (C472U in the IRES, C2034U encoding an S → F substitution at position 91 of VP3, and U2493C encoding an I → T substitution at position 6 of VP1) appear to be the main determinants of the attenuated phenotype (109, 126, 203)”

The critical attenuating mutations of the Sabin strains frequently revert well before nucleotide substitutions accumulate to the level of 1%.

“Indeed, the critical attenuating mutations of the Sabin strains frequently revert well before nucleotide substitutions accumulate to the level of 1% (126, 127, 228).”

The experimentally determined properties of VDPVs are not unique to VDPV isolates, as OPV-like polioviruses isolated from healthy individuals and VAPP patients may share some or all of these traits.

“While these experimentally determined properties may correlate with clinically relevant properties, they are not unique to VDPV isolates, as OPV-like polioviruses isolated from healthy individuals and VAPP patients may share some or all of these traits (126, 127, 133).”