Heterogeneity and recombination of foot-and-mouth disease virus during multi-strain coinfection of cattle

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

Submitted to: mSphere
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/29/2023
Publication Date: 4/24/2023
Citation: Stenfeldt, C., Fish, I., Meek, H., Arzt, J. 2023. Heterogeneity and recombination of foot-and-mouth disease virus during multi-strain coinfection of cattle. mSphere. 22;8(3):e0064322. https://doi.org/10.1128/msphere.00643-22.
DOI: https://doi.org/10.1128/msphere.00643-22

Interpretive Summary: Foot-and-mouth disease (FMD) is an important livestock disease. It is known that different variants of FMD virus (FMDV) may exchange genetic material if one animal is infected with two viruses at the same time. However, it has not previously been known where in the animal this process takes place. This current study shows how serial infections of cattle with two different serotypes of FMDV leads to rapid generation of new and different viruses in the upper respiratory tracts of infected animals. This finding is particularly relevant in relation to management of persistently infected FMDV carrier cattle that can maintain silent FMDV infection for months to years after an infection. Such carrier animals may function as mixing vessels that facilitate the emergence of recombinant FMDV strains in areas where multiple virus strains are in circulation. This information helps to protect USA livestock industries from an outbreak of FMDV.

Technical Abstract: Superinfection of cattle persistently infected with foot-and-mouth disease virus (FMDV), with a heterologous FMDV strain has been shown to generate novel recombinant viruses. In the current study, the pathogenesis events within specific tissues associated with FMDV coinfections were investigated in cattle that were subjected to either simultaneous or serial exposure to two distinct strains of FMDV. Both strains of FMDV (one each of serotypes O and A) were similarly localized to the nasopharyngeal mucosa during the early stages of infection. However, while no recombinant FMDV genomes were recovered from simultaneously coinfected cattle, inter-serotypic recombinants were isolated from nasopharyngeal tissue samples obtained at 48h after heterologous superinfection of a persistently infected FMDV carrier. Additionally, analysis of FMDV genomes obtained from replicate nasopharyngeal tissue samples demonstrated that adjacent segments of the mucosa were sometimes infected by distinct viruses, demonstrating a multifocal and heterogeneous distribution of FMDV infection during primary and persistent phases of infection. This work indicates that superinfection of FMDV carriers may be an important source of emergent recombinant strains of FMDV in areas where multiple strains are co-circulating.