Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/11/2018
Publication Date: 4/28/2018
Citation: Brito, B.P., Pauszek, S.J., Hartwig, E.J., Smoliga, G.R., Vu, L.T., Vu, P.P., Stenfeldt, C., Rodriguez, L.L., King, D.P., Knowles, N.J., Bachanek-Bankowska, K., Long, N.T., Dung, D.H., Arzt, J. 2018. A traditional evolutionary history of foot-and-mouth disease viruses in Southeast Asia challenged by analyses of non-structural protein coding sequences. Scientific Reports. 8:6472. https://doi.org/10.1038/s41598-018-24870-6.
DOI: https://doi.org/10.1038/s41598-018-24870-6

Interpretive Summary: Foot-and-mouth disease virus (FMDV) is a highly contagious disease of livestock, which is not present in the USA, but is present in Africa, Asia and South America. This virus can cause devastating economic losses if newly introduced into any country. The genetic differences of the virus traditionally have been studied using a small portion, just 8%, of the virus’s genetic material (genome). In this study we used the entire genome of the virus that encodes for viral proteins, to understand the evolutionary pattern of FMDV in Southeast Asia. The results of these analyses allowed us to understand potential recombination of different viruses, and relationships between different virus strains. The results suggest that recombination may be more likely among some strains given their ancestral relationships. This study, and the analytic approach used contributes to understanding new evolutionary aspects of the virus based on the full genome. Ultimately, this information contributes to improving preparedness for FMD outbreaks in the USA.

Technical Abstract: Molecular epidemiology and evolution of foot-and-mouth disease virus (FMDV) are widely studied using genomic sequences encoding VP1, the capsid protein containing the most relevant antigenic domains. Although sequencing of the full viral genome is not used as a routine diagnostic or surveillance tool, their availability in public repositories has increased over recent years, thereby motivating more detailed analyses. In the current study, we selected polyprotein (ORF) encoding sequences (n=96) available for five FMD virus lineages (A/ASIA/Sea-97, O/ME-SA/PanAsia, O/SEA/Mya-98, O/CATHAY, and Asia1/Group V) co-circulating in Southeast Asia to investigate whether there was evidence for intra- and inter-lineage recombination. We first determined putative recombination breakpoints detected by different algorithms. Subsequently, we used a Bayesian phylogenetic approach to estimate time divergence of the recombination-free genome regions. Phylogenetic analysis revealed a close relationship between O/Mya-98 and A/Sea-97 lineages in their non-structural protein (NSP) coding regions. Additionally, three specific mosaic viruses (recombinants) of lineage A/Sea97 and O/Mya98 were detected. Contrastingly, O/CATHAY virus capsids and NSP encoding sequences have evolved independently from other lineages. Analysis of intra-lineage recombination revealed different locations of breakpoint hotspot patterns within the genome of each lineage. This study provides new insights about the evolutionary interdependence of FMDV serotypes and lineages. Unveiling the evolutionary mechanisms of FMDV may contribute to understanding emergence of new lineages, and inform the risk posed by co-circulating lineages in FMD endemic countries and regions.