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Genetic determinants of cell type-specific poliovirus propagation in HEK 293 cells.

Publication ,  Journal Article
Campbell, SA; Lin, J; Dobrikova, EY; Gromeier, M
Published in: J Virol
May 2005

The ability of poliovirus to propagate in neuronal cells can be reduced by introducing appropriate nucleotide substitutions into the viral genome. Specific mutations scattered throughout the poliovirus genome yielded the live attenuated vaccine strains of poliovirus. Neuron-specific propagation deficits of the Sabin strains are partially encrypted within a confined region of the internal ribosomal entry site (IRES), which carries attenuating point mutations in all three serotypes. Recently, high levels of neurovirulence attenuation were achieved with genetically engineered polioviruses containing heterologous IRES elements. This is exemplified with poliovirus recombinants replicating under control of a human rhinovirus type 2 (HRV2) IRES element. We have carried out experiments delineating the genetic basis for neuronal IRES function. Neuronal dysfunction of the HRV2 IRES is determined mainly by IRES stem-loop domain V, the locus for attenuating point mutations within the Sabin strains. Neuronal incompetence associated with HRV2 IRES domain V is substantially more pronounced than that observed with the attenuating IRES point mutation of the Sabin serotype 1 vaccine strain. Mix-and-match recombination of polio and HRV2 IRES domain V suggests that the attenuation phenotype correlates with overall structural features rather than primary sequence. Our experiments have identified HEK 293 cells as a novel system for the study of neuron-specific replication phenotypes of poliovirus. This cell line, originally derived from embryonic human kidney, has recently been described to display neuronal characteristics. We report propagation properties in HEK 293 cells for poliovirus recombinants with attenuated neurovirulence in experimental animals that corroborate this observation.

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Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

May 2005

Volume

79

Issue

10

Start / End Page

6281 / 6290

Location

United States

Related Subject Headings

  • Virus Replication
  • Virulence
  • Virology
  • Species Specificity
  • Rhinovirus
  • Reassortant Viruses
  • Poliovirus
  • Nucleic Acid Conformation
  • Molecular Sequence Data
  • Humans
 

Citation

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ICMJE
MLA
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Campbell, S. A., Lin, J., Dobrikova, E. Y., & Gromeier, M. (2005). Genetic determinants of cell type-specific poliovirus propagation in HEK 293 cells. J Virol, 79(10), 6281–6290. https://doi.org/10.1128/JVI.79.10.6281-6290.2005
Campbell, Stephanie A., Jennifer Lin, Elena Y. Dobrikova, and Matthias Gromeier. “Genetic determinants of cell type-specific poliovirus propagation in HEK 293 cells.J Virol 79, no. 10 (May 2005): 6281–90. https://doi.org/10.1128/JVI.79.10.6281-6290.2005.
Campbell SA, Lin J, Dobrikova EY, Gromeier M. Genetic determinants of cell type-specific poliovirus propagation in HEK 293 cells. J Virol. 2005 May;79(10):6281–90.
Campbell, Stephanie A., et al. “Genetic determinants of cell type-specific poliovirus propagation in HEK 293 cells.J Virol, vol. 79, no. 10, May 2005, pp. 6281–90. Pubmed, doi:10.1128/JVI.79.10.6281-6290.2005.
Campbell SA, Lin J, Dobrikova EY, Gromeier M. Genetic determinants of cell type-specific poliovirus propagation in HEK 293 cells. J Virol. 2005 May;79(10):6281–6290.

Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

May 2005

Volume

79

Issue

10

Start / End Page

6281 / 6290

Location

United States

Related Subject Headings

  • Virus Replication
  • Virulence
  • Virology
  • Species Specificity
  • Rhinovirus
  • Reassortant Viruses
  • Poliovirus
  • Nucleic Acid Conformation
  • Molecular Sequence Data
  • Humans