Comparative Genomics of Foot-and-Mouth Disease Virus

Abstract

Here we present complete genome sequences, including a comparative analysis, of 103 isolates of foot-andmouth disease virus (FMDV) representing all seven serotypes and including the first complete sequences of the SAT1 and SAT3 genomes. The data reveal novel highly conserved genomic regions, indicating functional constraints for variability as well as novel viral genomic motifs with likely biological relevance. Previously undescribed invariant motifs were identified in the 5 and 3 untranslated regions (UTR), as was tolerance for insertions/deletions in the 5 UTR. Fifty-eight percent of the amino acids encoded by FMDV isolates are invariant, suggesting that these residues are critical for virus biology. Novel, conserved sequence motifs with likely functional significance were identified within proteins L pro , 1B, 1D, and 3C. An analysis of the complete FMDV genomes indicated phylogenetic incongruities between different genomic regions which were suggestive of interserotypic recombination. Additionally, a novel SAT virus lineage containing nonstructural proteinencoding regions distinct from other SAT and Euroasiatic lineages was identified. Insights into viral RNA sequence conservation and variability and genetic diversity in nature will likely impact our understanding of FMDV infections, host range, and transmission.

New insights into internal ribosome entry site elements relevant for viral gene expression

“…Site-directed substitutions in the FMDV GNRA motif led to a local reorganization of the apical region that allowed the identification of a second motif (Fernandez-Miragall et al, 2006), presumably encompassing the GNRA receptor. It is noteworthy that this motif is located in an invariant region of about 100 FMDV sequences (Carrillo et al, 2005) that can potentially form Watson-Crick pairs with nearby residues according to computer-folding programs. In spite of the high genetic variability of FMDV viral RNA (Domingo et al, 1992), sequence variability from field isolates shows rare substitutions in the GUAA sequence to GCAA or GCGA, always compatible with GNRA motifs.…”

“…A unique feature of the aphthovirus viral RNA is the presence of two initiation codons, conserved in all FMDV isolates (Carrillo et al, 2005), which are used to initiate translation of the leader (L) protein in two forms, Lab and Lb (Fig. 1, lower panel).…”

Foot and Mouth Disease Virus Genome

“…Furthermore, complete genome sequencing has enhanced the discovery of FMDV variability, sequence conservation and universal genetic motifs that affect its virulence and transmission. Complete genome sequence analysis of FMDV isolates collected during the August 2007 outbreaks in England identified the initial and intermediate sources of the outbreaks, demonstrating the value of complete sequence analysis when examining virus phylogeny, an accomplishment previously impossible using partial genomic sequences (14,15,16). …”

“…Interestingly, the location and nature of the genetic variation was not the same as in vitro-acquired differences (see ref. 31,32,33,34,37) Comparative genomics studies using full-length sequences representative of all seven serotypes have identified highly conserved genomic regions, indicating functional constraints for variability as well as as-yet undefined motifs with likely biological significance (14,34). At least 64% of all nt sites within the FMDV genome are susceptible to substitution, including compensatory substitutions.…”

Development of multiplex RT-PCR for detection and differentiationof foot-and-mouth disease virus O and A serotypes in Turkey

“…Although cross-immunity has not been observed among the serotypes, partial immunity has been reported among the subtypes (1-3). High mutation rates and quasispecies population structure in FMDV triggers many antigenically and genetically divergent strains within each serotype of the virus, all of which cause difficulties in control of the disease (4)(5)(6).…”