J Vet Sci.  2011 Dec;12(4):363-371. 10.4142/jvs.2011.12.4.363.

Molecular characterization of a 13-amino acid deletion in VP1 (1D) protein and novel amino acid substitutions in 3D polymerase protein of foot and mouth disease virus subtype A/Iran87

Affiliations
  • 1Department of Biotechnology, Razi Vaccine and Serum Research Institute, Karaj 3197619751, Iran. m.esmaelizad@rvsri.ir
  • 2Department of Quality Control, Razi Vaccine and Serum Research Institute, Karaj 3197619751, Iran.

Abstract

The nucleotide sequence of the VP1 (1D) and partial 3D polymerase (3Dpol) coding regions of the foot and mouth disease virus (FMDV) vaccine strain A/Iran87, a highly passaged isolate (~150 passages), was determined and aligned with previously published FMDV serotype A sequences. Overall analysis of the amino acid substitutions revealed that the partial 3Dpol coding region contained four amino acid alterations. Amino acid sequence comparison of the VP1 coding region of the field isolates revealed deletions in the highly passaged Iranian isolate (A/Iran87). The prominent G-H loop of the FMDV VP1 protein contains the conserved arginine-glycine-aspartic acid (RGD) tripeptide, which is a well-known ligand for a specific cell surface integrin. Despite losing the RGD sequence of the VP1 protein and an Asp26-->Glu substitution in a beta sheet located within a small groove of the 3Dpol protein, the virus grew in BHK 21 suspension cell cultures. Since this strain has been used as a vaccine strain, it may be inferred that the RGD deletion has no critical role in virus attachment to the cell during the initiation of infection. It is probable that this FMDV subtype can utilize other pathways for cell attachment.

Keyword

3Dpol protein; deletion; RGD; VP1 protein

MeSH Terms

Amino Acid Sequence
Amino Acid Substitution
Antigens, Viral/chemistry/*genetics/metabolism
Capsid Proteins/chemistry/*genetics/metabolism
Cloning, Molecular
Foot-and-Mouth Disease Virus/classification/*genetics/*metabolism
Gene Expression Regulation, Viral
Molecular Sequence Data
Phylogeny
Viral Nonstructural Proteins/chemistry/*genetics/metabolism

Figure

  • Fig. 1 Alignment of the translated amino acid sequences of the (A) VP1 and (B) 3D polymerase (3Dpol) genes. Dashes (-) represent absent amino acids. Differences in amino acids among the isolates are indicated by a single letter code. Red boxes indicate amino acid deletions and substitutions in the consensus sequence (A/Iran87) relative to the other isolates.

  • Fig. 2 Phylogenetic tree showing relationships among different A field viruses according to the (A) VP1 and (B) 3Dpol gene sequences. Lineages and bootstrap values are shown on the tree.

  • Fig. 3 (A) The predicted three-dimensional space-filling and worm style structures of the 3Dpol protein of the A/Iran87 isolate. Novel amino acid substitutions are marked in yellow. (B) The predicted three-dimensional VP1 structure of the A/Iran87 isolate determined by homology-based modeling. The arrow indicates 13-amino acid deletions including the arginineglycine-aspartic acid (RGD) sequence in the G-H loop.


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