Into the deep (sequence) of the foot-and-mouth disease virus gene pool: population bottlenecks and adaptation during infection in naïve and vaccinated cattle

Authors: FISH, IAN - Oak Ridge Institute For Science And Education (ORISE); STENFELDT, CAROLINA - Kansas State University; PALINSKI, RACHEL - Kansas State University; Pauszek, Steven; Arzt, Jonathan

Submitted to: mSphere
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/9/2020
Publication Date: 3/12/2020
Citation: Fish, I., Stenfeldt, C., Palinski, R.M., Pauszek, S.J., Arzt, J. 2020. Into the deep (sequence) of the foot-and-mouth disease virus gene pool: population bottlenecks and adaptation during infection in naïve and vaccinated cattle. mSphere. https://doi.org/10.3390/pathogens9030208.
DOI: https://doi.org/10.3390/pathogens9030208

Interpretive Summary: Foot-and-mouth disease (FMD) is a primary concern to agriculture in Asia and Africa, also imposing substantial costs related to surveillance and trade limitations affecting the whole world. The factors that contribute to foot-and-mouth disease virus (FMDV) persistence in cattle and its evolution are important topics, but not well-understood. This experimental study of foot-and-mouth disease virus in cattle explores the virus through detailed sampling and analytical methods in both vaccinated and non-vaccinated hosts. Significant differences were identified between the viruses asymptomatically infecting vaccinated animals and those causing acute disease in the non-vaccinated animals. These results can benefit vaccination programs and contribute to the understanding and prevention of persistent infection of cattle.

Technical Abstract: Foot-and-mouth disease virus (FMDV), like many RNA viruses, infects hosts as a population of closely related viruses referred to as a quasispecies. The behavior of this quasispecies has not been described in detail over the full course of infection in a natural host species. In this study, virus samples taken up to 35 days post experimental infection with FMDV A24-Cruzeiro in both vaccinated and non-vaccinated cattle were analyzed by deep-sequencing. Vaccination corresponded with significant differences in virus substitution rates, entropy, and evidence for adaptation. Variation detected during early infection was found to be inherited from the diversity of the source virus (inoculum), whereas after 12 days post infection (dpi) dominant viruses were defined by newly-acquired mutations. In most serially-sampled cattle, mutations conferring recognized fitness gain occurred within numerous genetic backgrounds, often associated with selective sweeps. Persistent infection always included multiple FMDV subpopulations, suggesting independently maintained foci of infection within the nasopharyngeal mucosa. While vaccination did not confer protection against subclinical or persistent FMDV infection, it was associated with very early bottlenecks which in turn reduced the subsequent capability for virus adaptation. This implies an added value for vaccination in control of foot-and-mouth disease. Viruses sampled from both animal cohorts encoded putative antigenic escape mutations. However, these mutations occurred during later stages of infection, at which time transmission between animals is unlikely to occur.