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Pathogens
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Foot-and-Mouth Disease Virus: Pathogenesis and Persistence
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Foot-and-Mouth Disease Virus: Pathogenesis and Persistence

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (25 January 2024) | Viewed by 13338

Special Issue Editors

Dr. Michael Eschbaumer

E-Mail Website
Guest Editor
Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, 17493 Greifswald, Insel Riems, Germany
Interests: foot-and-mouth disease; pathogenesis; persistent infection; diagnosis; prevention
Dr. Florian Pfaff

E-Mail Website
Guest Editor
Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, 17493 Greifswald-Insel Riems, Germany
Interests: virus discovery; viral populations; transcriptomics; next-generation sequencing; molecular evolution and phylogenetics
Dr. Christine Luttermann

E-Mail Website
Guest Editor
Institute for Immunology, Friedrich-Loeffler-Institut, 17493 Greifswald, Insel Riems, Germany
Interests: foot-and-mouth disease; viral interference with innate immune system; viral replication; vaccine development

Special Issue Information

Dear Colleagues,

Foot-and-mouth disease (FMD) remains a serious global threat to animal husbandry and free trade in animal products. Inactivated vaccines are being used successfully in the control of FMD in many parts of the world, but they have several well-known issues. Their production requires biological containment measures that are logistically challenging and cost-intensive, while their protective efficacy is often narrow and of short duration. In addition, these vaccines do not reliably protect against primary virus replication and persistent infection. Many infected ruminants will carry the virus in the nasopharyngeal cavity over a long time and the fear of contagion from carriers is a major obstacle to the implementation of vaccinate-to-live policies in free areas.

It has been shown recently that the controlled attenuation of FMDV by the targeted deletion or modification of virulence factors (e.g., the leader protease) can decrease the risks associated with the production of inactivated vaccines. More generally, a better understanding of the function of these viral factors in FMD pathogenesis can pave the way for the development and validation of stably attenuated viruses that may be used as live vaccines, potentially overcoming some of the disadvantages of inactivated formulations.

To this end, this Special Issue invites all submissions related to the pathogenesis of acute and persistent FMDV infection, with particular regard to virus attenuation by targeted alterations of the viral genome.

Dr. Michael Eschbaumer
Dr. Florian Pfaff
Dr. Christine Luttermann
Guest Editors

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Keywords

  • foot-and-mouth disease
  • pathogenesis
  • virulence factors
  • attenuation
  • persistent infection

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Published Papers (4 papers)

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Research

8 pages, 1018 KiB  
Communication
Efficacy of Binary Ethylenimine in the Inactivation of Foot-and-Mouth Disease Virus for Vaccine Production in South Korea
by Jae Young Kim, Sun Young Park, Jong Sook Jin, Dohyun Kim, Jong-Hyeon Park, Sang Hyun Park and Young-Joon Ko
Pathogens 2023, 12(6), 760; https://doi.org/10.3390/pathogens12060760 - 25 May 2023
Cited by 8 | Viewed by 2563
Abstract
Foot-and-mouth disease (FMD) vaccines must be produced in a biosafety level 3 facility, so the FMD virus (FMDV) must be completely inactivated after amplification. The inactivation kinetics of FMDV during vaccine antigen production were assessed by evaluating whether the viral titer dropped below [...] Read more.
Foot-and-mouth disease (FMD) vaccines must be produced in a biosafety level 3 facility, so the FMD virus (FMDV) must be completely inactivated after amplification. The inactivation kinetics of FMDV during vaccine antigen production were assessed by evaluating whether the viral titer dropped below 10−7 TCID50/mL within 24 h of binary ethyleneimine (BEI) treatment. This study dealt with four FMD vaccine candidate strains for the efficacy of BEI treatment at different concentrations and temperatures to determine the optimal inactivation condition of each virus. Two domestic isolates, O/SKR/Boeun/2017 (O BE) and A/SKR/Yeoncheon/2017 (A YC), and two recombinant viruses, PAK/44/2008 (O PA-2) and A22/Iraq/24/64 (A22 IRQ), were investigated. The O BE and A22 IRQ required 2 mM BEI at 26 °C and 0.5 mM BEI at 37 °C for complete inactivation. The O PA-2 and A YC required 2 mM BEI at 26 °C and 1 mM BEI at 37 °C. Crucially, the yield of FMD virus particles (146S) in the viral infection supernatant was higher (>4.0 µg/mL) than those previously reported; additionally, there was little antigen loss, even after 24 h of treatment with 3 mM BEI. Overall, it is considered economical to produce FMD vaccines using these four kinds of viruses; therefore, these candidate strains will be prioritized for the manufacture of FMD vaccines in South Korea. Full article
(This article belongs to the Special Issue Foot-and-Mouth Disease Virus: Pathogenesis and Persistence)
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21 pages, 762 KiB  
Article
Inferred Causal Mechanisms of Persistent FMDV Infection in Cattle from Differential Gene Expression in the Nasopharyngeal Mucosa
by James J. Zhu, Carolina Stenfeldt, Elizabeth A. Bishop, Jessica A. Canter, Michael Eschbaumer, Luis L. Rodriguez and Jonathan Arzt
Pathogens 2022, 11(8), 822; https://doi.org/10.3390/pathogens11080822 - 22 Jul 2022
Cited by 3 | Viewed by 2961
Abstract
Foot-and-mouth disease virus (FMDV) can persistently infect pharyngeal epithelia in ruminants but not in pigs. Our previous studies demonstrated that persistent FMDV infection in cattle was associated with under-expression of several chemokines that recruit immune cells. This report focuses on the analysis of [...] Read more.
Foot-and-mouth disease virus (FMDV) can persistently infect pharyngeal epithelia in ruminants but not in pigs. Our previous studies demonstrated that persistent FMDV infection in cattle was associated with under-expression of several chemokines that recruit immune cells. This report focuses on the analysis of differentially expressed genes (DEG) identified during the transitional phase of infection, defined as the period when animals diverge between becoming carriers or terminators. During this phase, Th17-stimulating cytokines (IL6 and IL23A) and Th17-recruiting chemokines (CCL14 and CCL20) were upregulated in animals that were still infected (transitional carriers) compared to those that had recently cleared infection (terminators), whereas chemokines recruiting neutrophils and CD8+ T effector cells (CCL3 and ELR+CXCLs) were downregulated. Upregulated Th17-specific receptor, CCR6, and Th17-associated genes, CD146, MIR155, and ThPOK, suggested increased Th17 cell activity in transitional carriers. However, a complex interplay of the Th17 regulatory axis was indicated by non-significant upregulation of IL17A and downregulation of IL17F, two hallmarks of TH17 activity. Other DEG suggested that transitional carriers had upregulated aryl hydrocarbon receptor (AHR), non-canonical NFκB signaling, and downregulated canonical NFκB signaling. The results described herein provide novel insights into the mechanisms of establishment of FMDV persistence. Additionally, the fact that ruminants, unlike pigs, produce a large amount of AHR ligands suggests a plausible explanation of why FMDV persists in ruminants, but not in pigs. Full article
(This article belongs to the Special Issue Foot-and-Mouth Disease Virus: Pathogenesis and Persistence)
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20 pages, 4546 KiB  
Article
Foot-and-Mouth Disease Virus Interserotypic Recombination in Superinfected Carrier Cattle
by Ian Fish, Carolina Stenfeldt, Edward Spinard, Gisselle N. Medina, Paul A. Azzinaro, Miranda R. Bertram, Lauren Holinka, George R. Smoliga, Ethan J. Hartwig, Teresa de los Santos and Jonathan Arzt
Pathogens 2022, 11(6), 644; https://doi.org/10.3390/pathogens11060644 - 3 Jun 2022
Cited by 13 | Viewed by 3332
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 [...] Read more.
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 associated virus–host interactions within an infected host have not been determined. We have previously reported the detection of interserotypic recombinant FMDVs in oropharyngeal fluid (OPF) samples of 42% (5/12) of heterologously superinfected FMDV 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 detected 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 have detectable antibodies at the time of infection. In vitro analysis of a plaque-purified recombinant virus demonstrated a growth rate comparable to its parental precursors, and measurement of its specific infectivity suggested that the recombinant virus 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. Full article
(This article belongs to the Special Issue Foot-and-Mouth Disease Virus: Pathogenesis and Persistence)
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14 pages, 3787 KiB  
Article
Degradation of Host Proteins and Apoptosis Induced by Foot-and-Mouth Disease Virus 3C Protease
by Jiamin Yi, Jiangling Peng, Jingjing Ren, Guoqiang Zhu, Yi Ru, Hong Tian, Dan Li and Haixue Zheng
Pathogens 2021, 10(12), 1566; https://doi.org/10.3390/pathogens10121566 - 30 Nov 2021
Cited by 4 | Viewed by 2971
Abstract
Foot-and-mouth disease (FMD), induced by the foot-and-mouth disease virus (FMDV), is a highly contagious disease of cloven-hoofed animals. Previous studies have reported that FMDV 3C protease could degrade multiple host proteins; however, the degradation mechanism mediated by FMDV 3C is still unclear. Here, [...] Read more.
Foot-and-mouth disease (FMD), induced by the foot-and-mouth disease virus (FMDV), is a highly contagious disease of cloven-hoofed animals. Previous studies have reported that FMDV 3C protease could degrade multiple host proteins; however, the degradation mechanism mediated by FMDV 3C is still unclear. Here, we found that transient expression of FMDV 3C degraded various molecules in NF-κB signaling in a dose-dependent manner, and the proteolytic activity of FMDV 3C is important for inducing degradation. Additionally, 3C-overexpression was associated with the induction of apoptosis. In this study, we showed that an apoptosis inhibitor CrmA abolished the ability of 3C to degrade molecules in NF-κB signaling. Further experiments using specific caspase inhibitors confirmed the irrelevance of caspase3, caspase8, and caspase9 activity for degradation induced by 3C. Altogether, these results suggest that FMDV 3C induces the widespread degradation of host proteins through its proteolytic activity and that the apoptosis pathway might be an important strategy to mediate this process. Further exploration of the relationship between apoptosis and degradation induced by 3C could provide novel insights into the pathogenic mechanisms of FMDV. Full article
(This article belongs to the Special Issue Foot-and-Mouth Disease Virus: Pathogenesis and Persistence)
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