Playing Whac-A-Mole With Polio

Viruses Are Cool #5
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There have been many recent news reports highlighting problems facing the polio eradication campaign in Africa. The global initiative to eradicate polio was launched in 1988 by the 41st World Health Assembly, with a deadline set for 2000. But now, 7 years past the deadline, Nigeria is experiencing outbreaks of vaccine-derived polio among non-immunized populations who contract the disease from revertant virus excreted by those who have been immunized.

Reversion of the polio vaccine strain to a virulent form is a risk associated with the live attenuated oral polio vaccine. But part of the reason for the recent outbreaks is incomplete vaccination of the population, which leaves significant numbers of non-immune individuals who are susceptible to infection with vaccine-derived virus. Sadly, the incomplete vaccination is largely due to suspicion of the vaccine, and these outbreaks are likely to exacerbate the situation by stoking fears.

For more than a year from mid-2003 the northern states stopped the vaccination programme altogether after rumours swept the country that the polio vaccine caused Aids and that it was all part of a western plot to sterilise Muslim girls. Many still believe these scare stories and its one of the main reasons why people still refuse to vaccinate their children.

However, a recent study published in PNAS calls into question whether polio eradication is possible at all. Eradication of a viral disease in humans requires the absence of an animal reservoir for the virus. For example, smallpox could be eradicated because there were no other organisms in which smallpox virus could replicate once the human population had been immunized. Although poliovirus does not have an animal reservoir, this study presents evidence for evolution of poliovirus from the related coxsackie virus, suggesting that coxsackie virus could serve as a reservoir for de novo speciation of poliovirus.

The three poliovirus serotypes, together with 11 coxsackie A viruses, form the human enterovirus C cluster (HEV-C) in family Picornaviridae and genus enterovirus. Despite their similarities, coxsackie and polioviruses have very different pathogenesis. Coxsackie virus causes a relatively benign upper respiratory disease whereas poliovirus can cause irreversible paralysis or even death. This difference in pathogenicity is primarily due to utilization of different cellular receptors by the two viruses--ICAM-1 for coxsackie virus and CD155 for poliovirus.

The authors performed phylogenetic analysis of the HEV-C viruses, and their data suggest that mutation of the coxsackie virus capsid led to a switch from using ICAM-1 as a receptor to using CD155, thus creating poliovirus. To confirm the directionality of the evolution, they engineered chimeric viruses containing either (1) poliovirus capsid with coxsackie virus replication proteins or (2) coxsackie virus capsid with poliovirus replication proteins. They found that Type 1 chimeras are viable and replicate well, whereas Type 2 chimeras are defective. This asymmetry in compatibility between coxsackie and polioviruses is consistent with evolution of the poliovirus capsid from coxsackie virus, and not the other way around. The authors also demonstrated generation of Type 1, but not Type 2, chimeric viruses by recombination following co-infection of cells with both coxsackie and polioviruses.

Together, these data indicate that modern polioviruses are derived from an ancestral poliovirus which emerged through mutation of the coxsackie virus capsid to enable utilization of the CD155 receptor. This, if true, would have serious implications for the campaign to eradicate polio. It would mean that the human population would have to be perpetually immunized since poliovirus could spontaneously "re-evolve" from the pool of coxsackie viruses, just like the pesky moles emerging from their holes in the old arcade game.

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