Evidence for emergence of diverse polioviruses from C-cluster coxsackie A viruses and implications for global poliovirus eradication.
The poliovirus (PV) eradication campaign is conducted on the premise that this virus, because of the lack of a zoonotic reservoir, will not reemerge once eradicated. This report examines the origin of PV using theoretical and experimental approaches. Our rooted phylogenetic analysis suggests a speciation of PV from a C-cluster coxsackie A virus (C-CAV) ancestor through mutation of the capsid that caused a receptor switch from intercellular adhesion molecule-1 to CD155, leading to a change of pathogenicity. This hypothesis is supported experimentally with chimeras generated from three different pairs of PV and C-CAV. Those carrying the PV capsid and the replication proteins of C-CAVs replicated well, whereas their reciprocal counterparts were either debilitated or dead. This phenomenon of asymmetry is observed also in recombinants between PV1 and C-CAV20, selected in tissue culture cells using a previously undescribed protocol. The recombinants are generated at frequencies of 10(-6) typical for PV interserotype recombination. Strikingly, they resemble genetically and phenotypically, including neurovirulence in CD155 transgenic mice, the large majority of circulating vaccine-derived PVs that have caused poliomyelitis outbreaks in different parts of the world. These data provide experimental evidence for C-CAVs being partners to PVs in generating diverse PV progeny by homologous recombination. They support speciation of a novel human pathogen (PV) from a pool of different human pathogens (C-CAVs). In a PV-free world without PV neutralizing antibodies, contemporary C-CAV, like their ancestor(s), could be fertile ground for a PV-like agent to emerge by mutation.
Jiang
Ping
P
Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, NY 11794-5222, USA.
Faase
Johan A J
JA
Toyoda
Hidemi
H
Paul
Aniko
A
Wimmer
Eckard
E
Gorbalenya
Alexander E
AE
D000818:Animals; D001483:Base Sequence; D014644:Genetic Variation / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010802:Phylogeny; D011051:Poliomyelitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology; D017955:Poliovirus / Q000235:genetics* / Q000472:pathogenicity; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D012641:Selection, Genetic
D008565:Membrane Proteins; D011991:Receptors, Virus; C066100:poliovirus receptor