Amino acid substitutions within the 2C coding sequence of Theiler's Murine Encephalomyelitis virus alter virus growth and affect protein distribution

Lindsay Murray, Garry A. Luke, Martin Denis Ryan, Thomas Wileman, Caroline Knox

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Theiler's murine encephalomyelitis virus (TMEV) was used to investigate the distribution of P2 proteins in host cells and examine the effect of amino acid substitutions in conserved residues of the 2C protein on virus growth. The distribution of viral proteins 2B, 2C and 2BC with marker proteins of the endoplasmic reticulum (ER) and/or Golgi suggest an association with membranes of the secretory pathway. Similar results were obtained for truncated 2C and 2BC proteins with C-terminal deletions suggesting that the N-terminal region of the 2C protein is important in dictating distribution patterns. The significance of the high degree of conservation of this 2C region throughout the Picornaviridae was investigated by substituting conserved amino acid residues for alanine to create six mutant strains. Substitution mutations E(8)A, W(18)A and W(29)A abolished the ability of the virus to induce cytopathic effect (CPE) in BHK-21 cells. K(14)A, R(4)A and 1(23)A delayed the onset and progression of CPE compared to the wildtype (WT) virus, and decreased virus yield. Immunofluorescence analysis of cells transiently expressing mutant 2C proteins revealed that the distribution of 2C was affected by substituting K(14), W(18) and 1(23) for alanine indicating that specific conserved residues in 2C dictate protein distribution and virus growth. (C) 2009 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)74-82
Number of pages9
JournalVirus Research
Volume144
Issue number1-2
DOIs
Publication statusPublished - Sept 2009

Keywords

  • Cytopathic effect
  • Picornavirus
  • Protein 2C
  • Mutation
  • POLIOVIRUS REPLICATION COMPLEX
  • COXSACKIEVIRUS 2B PROTEIN
  • MEMBRANE ASSOCIATION
  • ENDOPLASMIC-RETICULUM
  • RNA-SYNTHESIS
  • AMPHIPATHIC HELIX
  • VIRAL-PROTEINS
  • MATRIX PROTEIN
  • GOLGI-COMPLEX
  • INDUCTION

Fingerprint

Dive into the research topics of 'Amino acid substitutions within the 2C coding sequence of Theiler's Murine Encephalomyelitis virus alter virus growth and affect protein distribution'. Together they form a unique fingerprint.

Cite this