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Research Project: Intervention Strategies to Support the Global Control and Eradication of Foot-and-Mouth Disease Virus (FMDV)

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

item Arzt, Jonathan
item FISH, IAN - Oak Ridge Institute For Science And Education (ORISE)
item Pauszek, Steven
item JOHNSON, SHANNON - Los Alamos National Research Laboratory
item CHAIN, PATRICK - Los Alamos National Research Laboratory
item RAI, DEVENDRA - University Of Minnesota
item Rieder, Aida - Elizabeth
item GOLDBERG, TONY - University Of Wisconsin
item Rodriguez, Luis
item STENFELDT, CAROLINA - University Of Minnesota

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/5/2019
Publication Date: 4/25/2019
Citation: Arzt, J., Fish, I., Pauszek, S.J., Johnson, S.L., Chain, P.S., Rai, D.K., Rieder, A.E., Goldberg, T.L., Rodriguez, L.L., Stenfeldt, C. 2019. The evolution of a super-swarm of foot-and-mouth disease virus in cattle. Virology.

Interpretive Summary: Foot-and-mouth disease virus (FMDV) is responsible for the most costly livestock disease on the planet, greatly limiting international trade in animal products. Cattle, pigs and other common domesticated and wild animals are susceptible to the disease. Understanding how the virus changes over time (evolves) both within hosts and through transmission chains is of central importance for vaccine development, vaccination and quarantine strategies and trade regulations. FMDV changes very rapidly but the factors and mechanisms responsible are very poorly understood. In order to better understand the virus evolution, the current study analyzed virus sampled from 13 FMDV-infected cattle over the course of 35 days. This study revealed an unexpected mechanism of evolution where new FMDV types appeared by emerging from other FMD strains; this process was called “minority haplotype emergence”. This mechanism of evolution is most pronounced during early disease, when cattle are most infectious. In addition, different evolutionary patterns were identified when comparing vaccinated to non-vaccinated cattle. These findings instruct both vaccine development and the study of disease outbreaks and ultimately may lead to enhanced protection of US livestock herds from FMD.

Technical Abstract: Virus evolution is generally described as a combination of drift, mutation, and selection within hosts followed by fixation of new variants that are subsequently transmitted to new hosts. The current study investigated the mechanisms contributing to within-host evolution of foot-and-mouth disease virus (FMDV) in a natural host species (cattle). Consensus-level genomic changes across the entire FMDV coding region were characterized through three stages of infection - early, transitional, and persistent (carrier) - in vaccinated and non-vaccinated cattle. The overall conclusion was that viral evolution occurred via a combination of two mechanisms: emergence of full genomic minority haplotypes, and concurrent continuous point mutation. Phylogenetic analysis indicated that individual animals were infected with multiple distinct haplogroups that were pre-existent within the ancestral inoculum that was 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. These insights into FMDV population dynamics have direct implications for molecular epidemiology and vaccine-development.