title: Poliovirus tropism and attenuation are determined after internal ribosome entry.
abstract: Poliovirus replication is limited to a few organs, including the brain and spinal cord. This restricted tropism may be a consequence of organ-specific differences in translation initiation by the poliovirus internal ribosome entry site (IRES). A C-to-U mutation at base 472 in the IRES of the Sabin type 3 poliovirus vaccine strain, known to attenuate neurovirulence, may further restrict tropism by eliminating viral replication in the CNS. To determine the relationship between IRES-mediated translation and poliovirus tropism, recombinant human adenoviruses were used to express bicistronic mRNAs in murine organs. The IRESs of poliovirus, the cardiotropic coxsackievirus B3 (CVB3), and the hepatotropic hepatitis C virus (HCV) mediate translation in many organs, including those that do not support viral replication. A translation defect associated with the Sabin type 3 IRES was observed in all organs examined. Poliovirus type 1 and recombinant polioviruses dependent on the IRES of CVB3 or HCV replicate in the CNS of mice and cause paralysis. Although the type 3 Sabin strain is an effective vaccine, polioviruses with a U at base 472 of the IRES cause paralysis in newborn mice. Tropism of wild-type and vaccine strains of poliovirus is therefore determined after internal ribosome entry.
authors.affiliation: Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Kauder
authors.forename: Vincent R
authors.initials: VR
authors.lastname: Racaniello
mesh_terms: D020121:5' Untranslated Regions; D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D029822:Enterovirus B, Human / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009690:Nucleic Acid Conformation; D011051:Poliomyelitis; D017955:Poliovirus / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D011055:Poliovirus Vaccine, Oral; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000737:chemistry; D012045:Regulatory Sequences, Nucleic Acid; D012270:Ribosomes / Q000378:metabolism*; D015996:Survival Rate; D014779:Virus Replication
chemical_list: D020121:5' Untranslated Regions; D011055:Poliovirus Vaccine, Oral; D012367:RNA, Viral