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Genetic adaptation to untranslated region-mediated enterovirus growth deficits by mutations in the nonstructural proteins 3AB and 3CD.

Publication ,  Journal Article
Florez de Sessions, P; Dobrikova, E; Gromeier, M
Published in: J Virol
August 2007

Both untranslated regions (UTRs) of plus-strand RNA virus genomes jointly control translation and replication of viral genomes. In the case of the Enterovirus genus of the Picornaviridae family, the 5'UTR consists of a cloverleaf-like terminus preceding the internal ribosomal entry site (IRES) and the 3' terminus is composed of a structured 3'UTR and poly(A). The IRES and poly(A) have been implicated in translation control, and all UTR structures, in addition to cis-acting genetic elements mapping to the open reading frame, have been assigned roles in RNA replication. Viral UTRs are recognized by viral and host cell RNA-binding proteins that may co-determine genome stability, translation, plus- and minus-strand RNA replication, and scaffolding of viral replication complexes within host cell substructures. In this report, we describe experiments with coxsackie B viruses with a cell type-specific propagation deficit in Sk-N-Mc neuroblastoma cells conferred by the combination of a heterologous IRES and altered 3'UTR. Serial passage of these constructs in Sk-N-Mc cells yielded genetic adaptation by mutations within the viral nonstructural proteins 3A and 3C. Our data implicate 3A and/or 3C or their precursors 3AB and/or 3CD in a functional complex with the IRES and 3'UTR that drives viral propagation. Adaptation to neuroblastoma cells suggests an involvement of cell type-specific host factors or the host cell cytoplasmic milieu in this phenomenon.

Duke Scholars

Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

August 2007

Volume

81

Issue

16

Start / End Page

8396 / 8405

Location

United States

Related Subject Headings

  • Virus Replication
  • Virology
  • Viral Proteins
  • Viral Nonstructural Proteins
  • Untranslated Regions
  • RNA, Viral
  • Nucleic Acid Conformation
  • Mutation
  • Molecular Sequence Data
  • Humans
 

Citation

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Florez de Sessions, P., Dobrikova, E., & Gromeier, M. (2007). Genetic adaptation to untranslated region-mediated enterovirus growth deficits by mutations in the nonstructural proteins 3AB and 3CD. J Virol, 81(16), 8396–8405. https://doi.org/10.1128/JVI.00321-07
Florez de Sessions, Paola, Elena Dobrikova, and Matthias Gromeier. “Genetic adaptation to untranslated region-mediated enterovirus growth deficits by mutations in the nonstructural proteins 3AB and 3CD.J Virol 81, no. 16 (August 2007): 8396–8405. https://doi.org/10.1128/JVI.00321-07.
Florez de Sessions, Paola, et al. “Genetic adaptation to untranslated region-mediated enterovirus growth deficits by mutations in the nonstructural proteins 3AB and 3CD.J Virol, vol. 81, no. 16, Aug. 2007, pp. 8396–405. Pubmed, doi:10.1128/JVI.00321-07.

Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

August 2007

Volume

81

Issue

16

Start / End Page

8396 / 8405

Location

United States

Related Subject Headings

  • Virus Replication
  • Virology
  • Viral Proteins
  • Viral Nonstructural Proteins
  • Untranslated Regions
  • RNA, Viral
  • Nucleic Acid Conformation
  • Mutation
  • Molecular Sequence Data
  • Humans