Simultaneous and staggered footand-mouth disease virus coinfection of cattle

Authors: Arzt, Jonathan; Bertram, Miranda; FISH, IAN - Oak Ridge Institute For Science And Education (ORISE); Smoliga, George; Hartwig, Ethan; PAUSZEK, STEVEN - Animal And Plant Health Inspection Service (APHIS); Diaz San Segundo, Fayna; SITT, TATJANA - University Of Kansas; Rieder, Aida - Elizabeth; STENFELDT, CAROLINA - University Of Kansas

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/23/2021
Publication Date: 9/29/2021
Citation: Arzt, J., Bertram, M.R., Fish, I., Smoliga, G.R., Hartwig, E.J., Pauszek, S., Diaz San Segundo, F.C., Sitt, T., Rieder, A.E., Stenfeldt, C. 2021. Simultaneous and staggered footand-mouth disease virus coinfection of cattle. Journal of Virology. https://doi.org/10.1128/JVI.01650-21.
DOI: https://doi.org/10.1128/JVI.01650-21

Interpretive Summary: Foot-and-mouth disease (FMD) is a viral infection of livestock of critical socioeconomic importance. Field studies from areas with FMD suggest that animals can be infected by more than one type of FMD virus (FMDV) at the same time. This could potentially lead to emergence of new viral strains as the viruses may recombine. The current study was carried out to investigate the mechanisms of FMD virus (FMDV) co-infections under controlled conditions. Our findings confirmed that cattle could be simultaneously infected by two distinct types of FMDV, with different outcomes depending on the timing of exposure to the two different viruses. Key findings include the discovery of viral recombination giving rise to a mixed FMDV strain in the upper respiratory tract of a double-infected animal, as well as of apparent clearance of a persistent FMDV infection resulting from super-infection with a different virus.

Technical Abstract: Foot-and-mouth disease (FMD) field studies have suggested the occurrence of simultaneous infection of individual hosts by multiple virus strains; however, the pathogenesis of foot-and-mouth disease virus (FMDV) coinfections is largely unknown. In the current study, groups of cattle were experimentally exposed to two FMDV strains of different serotypes (O and A). One cohort was subjected to simultaneous infection by both viruses, while additional cohorts were initially infected with FMDV serotype A and subsequently challenged with FMDV serotype O, at 21 or 35 days post initial infection. Coinfections were confirmed, both in the form of acute infection with both viruses concurrently detected in blood, lesions, and secretions, and as overlapping super-infections during which convalescent animals with persistent subclinical FMDV infection of the upper respiratory tract were re-infected with a non-homologous virus. Staggering virus exposure by 21 days conferred clinical protection in six of eight cattle, which were subclinically infected but protected against clinical FMD following the heterologous virus challenge. This effect was transient, as all animals challenged at 35 days post initial infection developed fulminant FMD. The majority of cattle maintained persistent infection with one of the two viruses while clearing the other. However, four animals that were challenged at 35 days post initial infection cleared both viruses within 35 days of the second exposure. Analysis of viral genomes confirmed one inter-serotypic recombination event in the upper respiratory tract of a superinfected animal, whereas there was no evidence of viral recombination in the acutely co-infected cattle.