Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/18/2005
Publication Date: 5/1/2005
Citation: Carrillo, C., Tulman, E., Delhon, G., Lu, Z., Vagnozzi, A., Kutish, G.F., Rock, D.L. 2005. Comparative Genomics of Foot-and-Mouth Disease Virus. Journal of Virology. 79(10)P.6487-6504.
Interpretive Summary: The limited number of complete FMDV genome sequences currently available prevents comparative analysis and the association of specific viral genotypes with significant biological traits. Here one hundred and four complete FMDV genome sequences representing all seven serotypes were obtained. Comparative analysis of all genome sequences did allow to quantify and characterize genetic conservation and which genomic regions can be used as indicators of selective pressures. We also describe mutation deleterious motifs that can be explored to attenuate the virus virulence as well as areas that might be tolerant to introduction of foreign sequences as markers for a putative vaccine. Viral genomic features with potential diagnostic, epidemiological and forensic value were identified.
Technical Abstract: Here we presently complete genome sequences, with comparative analysis, of 103 isolates of foot-and-mouth disease virus (FMDV), representing all seven serotypes and including the first complete sequences of SAT1 and SAT3 genomes. The data revealed 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 indels in the 5' UTR. Fifty-eight percent of the amino acids encoded by FMDV isolates were invariant, suggesting these residues are critical for virus biology. Novel, conserved sequence motifs of likely functional significance were identified within proteins Lpro, 1B, 1D, and 3C. Analysis of complete FMDV genomes indicated phylogenetic incongruencies between different genomic regions suggestive of interserotypic recombination. Additionally, a novel SAT virus lineage containing nonstructural protein-encoding 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 understanding of FMDV infection, host range, and transmission.