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Title: Differential mosaicism of recombinant foot-and-mouth disease viruses associated with the order of exposure to two heterologous virus strainsAuthor
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STENFELDT, CAROLINA - Kansas State University |
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FISH, IAN - Kansas State University |
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RODRIGUEZ-CALZADA, MONICA - Oak Ridge Institute For Science And Education (ORISE) |
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RICHT, JUERGEN - Kansas State University |
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Arzt, Jonathan |
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Medina, Gisselle |
Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 1/16/2025 Publication Date: 2/11/2025 Citation: Stenfeldt, C., Fish, I., Rodriguez-Calzada, M., Richt, J., Arzt, J., Medina, G.N. 2025. Differential mosaicism of recombinant foot-and-mouth disease viruses associated with the order of exposure to two heterologous virus strains. Journal of Virology. 99(3). Article e02213-24. https://doi.org/10.1128/jvi.02213-24. DOI: https://doi.org/10.1128/jvi.02213-24 Interpretive Summary: Foot-and-mouth disease (FMD) is an important livestock disease. It is known that different variants of FMD virus (FMDV) may recombine if one animal is infected with two viruses at the same time. This current study demonstrates that the order in which animals are exposed to the same two viruses influences the structure of the recombinant viruses that will form. 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. Technical Abstract: Evidence from both field- and experimental studies suggest that recombination is a common feature in the evolution of foot-and-mouth disease virus (FMDV). Recent studies have demonstrated that heterologous superinfection of cattle persistently infected with FMDV leads to rapid generation of inter-serotypic recombinant viruses in the upper respiratory tract mucosa. The current study demonstrates that subsequent to sequential superinfection with FMDV strains A24 Cruzeiro and O1 Manisa, the order of exposure substantially influenced the mosaicism of resultant recombinant viruses. There was no apparent competitive advantage of either parental virus. However, recovered recombinant viruses from 6 of 7 animals had gained, or re-gained through multiple recombination events, the capsid-coding sequence of FMDV O1 Manisa despite the presence of high titers of neutralizing antibodies against that virus. Additionally, a sub-genomic region of particularly high amino acid diversity, spanning the 3’ portion of 3A through 3B, was derived from FMDV A24 in most of the recovered recombinants. Although FMDV recombinants were isolated from oropharyngeal fluid samples from 7 of 12 experimental animals following superinfection at 21 days post initial infection, there was no detection of recombinant viruses in blood or lesions in the subset of animals that developed clinical FMD during superinfection. Overall, these findings confirm the high frequency at which FMDV recombination occurs when persistently infected carriers are exposed to a heterologous virus and reaffirm that superinfection of carriers should be considered as a source of FMDV genetic diversity in endemic regions. |