Research Article: The evolution of a super-swarm of foot-and-mouth disease virus in cattle

Date Published: April 25, 2019

Publisher: Public Library of Science

Author(s): Jonathan Arzt, Ian Fish, Steven J. Pauszek, Shannon L. Johnson, Patrick S. Chain, Devendra K. Rai, Elizabeth Rieder, Tony L. Goldberg, Luis L. Rodriguez, Carolina Stenfeldt, Naomi Forrester.


Foot-and-mouth disease (FMD) is a highly contagious viral disease that severely impacts global food security and is one of the greatest constraints on international trade of animal products. Extensive viral population diversity and rapid, continuous mutation of circulating FMD viruses (FMDVs) pose significant obstacles to the control and ultimate eradication of this important transboundary pathogen. The current study investigated mechanisms contributing to within-host evolution of FMDV in a natural host species (cattle). Specifically, vaccinated and non-vaccinated cattle were infected with FMDV under controlled, experimental conditions and subsequently sampled for up to 35 days to monitor viral genomic changes as related to phases of disease and experimental cohorts. Consensus-level genomic changes across the entire FMDV coding region were characterized through three previously defined stages of infection: early, transitional, and persistent. The overall conclusion was that viral evolution occurred via a combination of two mechanisms: emergence of full-genomic minority haplotypes from within the inoculum super-swarm, and concurrent continuous point mutations. Phylogenetic analysis indicated that individuals were infected with multiple distinct haplogroups that were pre-existent within the ancestral inoculum used to infect all animals. Multiple shifts of dominant viral haplotype took place during the early and transitional phases of infection, whereas few shifts occurred during persistent infection. Overall, this work suggests that the establishment of the carrier state is not associated with specific viral genomic characteristics. These insights into FMDV population dynamics have important implications for virus sampling methodology and molecular epidemiology.

Partial Text

Foot-and-mouth disease (FMD) is a highly contagious viral disease that affects wild and domestic even-toed ruminants [1, 2]. FMD is a major global concern for livestock owners and managers, and the disease has substantial impact on regulation of international trade in animal products [3]. The classical signs of disease include oral and pedal vesicles and erosions, often associated with lameness, pyrexia, and obtundation [2, 4]. The causative agent, FMD virus (FMDV) is extremely contagious and disseminates rapidly amongst susceptible animals. Although the disease is rarely fatal, FMD-endemic regions incur substantial economic burdens associated with production losses and disease control [5]. Sporadic outbreaks in countries that are normally free from FMD result in costly mediations including culling of large numbers of animals and livestock movement restrictions as well as massive economic losses due to restrictions on trade in animal products.

In order to investigate FMDV evolution within natural hosts, cattle were experimentally infected with a complex, heterogeneous inoculum by a simulated natural route, after which progeny virus samples were collected over the course of 35 days post inoculation. Analysis of the virus consensus sequences obtained during different phases of infection suggested that at least two distinct processes contribute to within-host FMDV genomic changes: 1) conventional molecular evolution characterized by selection acting upon individual, de novo nucleotide substitutions and/or resultant amino acid changes, and 2) emergence and regression of full-genome minority haplogroup members over the course of infection.




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