Foot-and-Mouth Disease virus interserotypic recombination in superinfected carrier cattle

Authors: FISH, IAN - Oak Ridge Institute For Science And Education (ORISE); Bertram, Miranda; STENFELDT, CAROLINA - Kansas State University; Smoliga, George; Hartwig, Ethan; Holinka-Patterson, Lauren; De Los Santos, Teresa; Spinard Iii, Edward; Medina, Gisselle; Arzt, Jonathan; Azzinaro, Paul

Submitted to: Pathogens
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/30/2022
Publication Date: 6/3/2022
Citation: Fish, I., Bertram, M.R., Stenfeldt, C., Smoliga, G.R., Hartwig, E.J., Holinka-Patterson, L.G., De Los Santos, T.B., Spinard III, E.J., Medina, G.N., Arzt, J., Azzinaro, P.A. 2022. Foot-and-Mouth Disease virus interserotypic recombination in superinfected carrier cattle. Pathogens. https://doi.org/10.3390/pathogens11060644.
DOI: https://doi.org/10.3390/pathogens11060644

Interpretive Summary: Viruses can swap genetic information in a process called recombination, which leads to evolution and new, distinct viruses. For foot-and-mouth disease virus (FMDV), recombination is known to occur, but has never been demonstrated experimentally within an infected animal. This study describes work by ARS/USDA scientists, which shows FMDV recombination in cattle for the first time. Specifically, viruses were shown to recombine frequently and rapidly in the upper respiratory tract of cattle during the phase when a late stage infection was further complicated by introduction of a new virus. Understanding the conditions associated with recombination such as location in the animal, stage of disease, and history of virus exposure will contribute to development of improved vaccines to protect US animal herds and agriculture.

Technical Abstract: Viral recombination contributes to the emergence of novel strains with the potential for altered host range, transmissibility, virulence and immune evasion. For foot-and-mouth disease virus (FMDV), cell culture experiments and phylogenetic analyses of field samples have demonstrated the occurrence of recombination. However, the frequency of recombination and necessary virus-host interactions within an infected host have not been determined. We have previously reported the detection of interserotypic recombinant FMDV in oropharyngeal fluid (OPF) samples of 42% (5/12) of superinfected carrier cattle. The present investigation consists of a detailed analysis of the virus populations in these samples including identification and characterization of additional interserotypic minority recombinants. In every animal in which recombination was detected, recombinant viruses were identified in the OPF at the earliest sampling point after superinfection. Some recombinants remained dominant until the end of the experiment, whereas others were outcompeted by parental strains. Genomic analysis of recombinants suggests host immune pressure as a major driver of recombinant emergence as all recombinants had capsid-coding regions derived from the superinfecting virus to which the animals did not yet have antibodies. In vitro analysis of a plaque purified recombinant virus demonstrated comparable growth rate compared to its parental precursors, and measurement of specific infectivity suggested that the recombinant incurred no penalty in packaging its new chimeric genome. These findings have important implications for the potential role of persistently infected carriers in FMDV ecology and the emergence of novel strains.