Document Detail


A host-specific, temperature-sensitive translation defect determines the attenuation phenotype of a human rhinovirus/poliovirus chimera, PV1(RIPO).
MedLine Citation:
PMID:  21561914     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
By using a rhinosvirus/poliovirus type 1 chimera, PV1(RIPO), with the cognate internal ribosome entry site (IRES) of human rhinovirus type 2 (HRV2), we set out to shed light on the mechanism by which this variant expresses its attenuated phenotype in poliovirus-sensitive, CD155 transgenic (tg) mice and cynomolgus monkeys. Here we report that replication of PV1(RIPO) is restricted not only in human cells of neuronal origin, as was reported previously, but also in cells of murine origin at physiological temperature. This block in replication was enhanced at 39.5°C but, remarkably, it was absent at 33°C. PV1(RIPO) variants that overcame the replication block were derived by serial passage under restrictive conditions in either mouse cells or human neuronal cells. All adapting mutations mapped to the 5'-nontranslated region of PV1(RIPO). Variants selected in mouse cells, but not in human neuronal cells, exhibited increased mouse neurovirulence in vivo. The observed strong mouse-specific defect of PV1(RIPO) at nonpermissive temperature correlated with the translational activity of the HRV2 IRES in this chimeric virus. These unexpected results must be kept in mind when poliovirus variants are tested in CD155 tg mice for their neurovirulent potential, particularly in assays of live attenuated oral poliovirus vaccine lots. Virulence may be masked by adverse species-specific conditions in mouse cells that may not allow accurate prediction of neurovirulence in the human host. Thus, novel poliovirus variants in line for possible development of human vaccines must be tested in nonhuman primates.
Authors:
Nusrat Jahan; Eckard Wimmer; Steffen Mueller
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-05-11
Journal Detail:
Title:  Journal of virology     Volume:  85     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-23     Completed Date:  2011-09-15     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7225-35     Citation Subset:  IM    
Affiliation:
Department of Molecular Genetics and Microbiology, Life Sciences Building, Stony Brook University, Stony Brook, NY 11794-5222, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
DNA Primers
Humans
Mice
Phenotype
Poliovirus / genetics,  physiology*
Protein Biosynthesis*
Reverse Transcriptase Polymerase Chain Reaction
Rhinovirus / genetics,  physiology*
Temperature*
Virus Replication
Grant Support
ID/Acronym/Agency:
5R01AI03948508/AI/NIAID NIH HHS; 5R37AI01512233/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers
Comments/Corrections

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