Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 4/1/2005
Publication Date: 5/23/2005
Citation: Carrillo, C., Lu, Z., Tulman, E., Vagnozzi, A., Delhon, G., Kutish, G.F., Rock, D.L. 2005. Comparative Genomics of Foot-and-Mouth Disease Virus. European Study Group on the Molecular Biology of Picornaviruses. P. I02.
Technical Abstract: Foot-and-mouth disease virus (FMDV), like other Picornaviruses, contains a positive sense, single stranded RNA genome of approximately 8.4 kb that is directly translated into a single polyprotein and cleaved, post-translationally, to render mature viral proteins. Currently, little is known regarding the motecular aspects of FMDV pathogenesis, including the genetic and molecular mechanisms underlying viral virulence and host rage. As for other microorganisms, comparative genomics may be of use to identify and characterize pathogen virulence, host range and immune evasion mechanisms, targets that may be exploited to improve vaccine design or to develope novel intervention/therapeutic approaches. Here we present the comparative analysis of one hundred and four full-lengh FMDV genome sequences representing all seven serotypes and an unprecedented widely variation of isolates. The results did allow to quantify and characterize genetic conservation and which genomic regions can be used as indicators of selective pressures. 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 LEADER, 1B, 1D, and 3C. 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. The present complete genome sequences include the first complete sequences of SAT1 and SAT3 genomes. Phylogenetic analysis indicated substantial 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. Finally, previously unrecognized importance of recombination in FMDV epidemiology, will significantly impact the understanding of FMDV genome variability, evolution and ecology.