TY - JOUR

T1 - Selection of functional 2A sequences within foot-and-mouth disease virus; requirements for the NPGP motif with a distinct codon bias

AU - Kjær, Jonas

AU - Belsham, Graham J

N1 - © 2018 Kjær and Belsham; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

PY - 2018/1

Y1 - 2018/1

N2 - Foot-and-mouth disease virus (FMDV) has a positive-sense ssRNA genome including a single, large, open reading frame. Splitting of the encoded polyprotein at the 2A/2B junction is mediated by the 2A peptide (18 residues long), which induces a nonproteolytic, cotranslational "cleavage" at its own C terminus. A conserved feature among variants of 2A is the C-terminal motif N16P17G18/P19, where P19 is the first residue of 2B. It has been shown previously that certain amino acid substitutions can be tolerated at residues E14, S15, and N16 within the 2A sequence of infectious FMDVs, but no variants at residues P17, G18, or P19 have been identified. In this study, using highly degenerate primers, we analyzed if any other residues can be present at each position of the NPG/P motif within infectious FMDV. No alternative forms of this motif were found to be encoded by rescued FMDVs after two, three, or four passages. However, surprisingly, a clear codon preference for the wt nucleotide sequence encoding the NPGP motif within these viruses was observed. Indeed, the codons selected to code for P17 and P19 within this motif were distinct; thus the synonymous codons are not equivalent.

AB - Foot-and-mouth disease virus (FMDV) has a positive-sense ssRNA genome including a single, large, open reading frame. Splitting of the encoded polyprotein at the 2A/2B junction is mediated by the 2A peptide (18 residues long), which induces a nonproteolytic, cotranslational "cleavage" at its own C terminus. A conserved feature among variants of 2A is the C-terminal motif N16P17G18/P19, where P19 is the first residue of 2B. It has been shown previously that certain amino acid substitutions can be tolerated at residues E14, S15, and N16 within the 2A sequence of infectious FMDVs, but no variants at residues P17, G18, or P19 have been identified. In this study, using highly degenerate primers, we analyzed if any other residues can be present at each position of the NPG/P motif within infectious FMDV. No alternative forms of this motif were found to be encoded by rescued FMDVs after two, three, or four passages. However, surprisingly, a clear codon preference for the wt nucleotide sequence encoding the NPGP motif within these viruses was observed. Indeed, the codons selected to code for P17 and P19 within this motif were distinct; thus the synonymous codons are not equivalent.

KW - Amino Acid Sequence

KW - Amino Acid Substitution

KW - Animals

KW - Base Sequence

KW - Cell Line

KW - Codon

KW - Cricetinae

KW - Foot-and-Mouth Disease Virus/chemistry

KW - Viral Proteins/chemistry

U2 - 10.1261/rna.063339.117

DO - 10.1261/rna.063339.117

M3 - Journal article

C2 - 29042507

VL - 24

SP - 12

EP - 17

JO - RNA

JF - RNA

SN - 1355-8382

ER -