• Journal of Life Science
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• v.30 no.3
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• pp.285-290
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• 2020

Foot-and-mouth disease virus (FMDV), a member of the genus Aphthovirus in the Picornaviridae family, affects wild and domesticated ruminants and pigs. FMDV causes various clinical symptoms, including severe inflammation in infected tissue. Genome RNA of FMDV shows a positive single-strand chain approximately 8.3 kb long and encodes a single long open reading frame (ORF). The ORF is translated into structural and non-structural proteins by viral proteases. The FMDV 2C protein is one of the non-structural proteins encoded by FMDV and plays a critical role in FMD pathogenesis, including inflammation, apoptosis, and viral replication. In this study, we examined whether FMDV 2C induces intracellular expression of pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). FMDV 2C expression in pig IBRS-2 cells increased mRNA and protein expression of TNFα at the transcriptional level via activation of TNFα promoter. Treatment with 4-phenylbutyric acid, an endoplasmic reticulum (ER) stress reducer, decreased TNFα expression induced by FMDV 2C. Activating transcription factor 4 (ATF4), a transcription factor mediating ER stress response, induced transactivation of TNFα promoter and expression of mRNA and protein of TNFα. However, the dominant negative mutant of ATF4 did not induce FMDV 2C-mediated TNFα expression. The results indicate that FMDV 2C protein increases clinical inflammation via ATF4-mediated TNFα expression and is associated with ER stress induction.

• Journal of Life Science
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• v.30 no.11
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• pp.947-955
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• 2020

The foot-and-mouth disease virus (FMDV), a member of the Aphthovirus genus in the Picornaviridae family, affects wild and domesticated ruminants and pigs. During replication of the FMDV RNA (ribonucleic acid) genome, FMDV-encoding RNA polymerase 3D acts in a highly location-specific manner. This suggests that specific RNA structures recognized by 3D polymerase within non-coding regions of the FMDV genome assist with binding during replication. One such region is the cis-acting replication element (CRE), which functions as a template for RNA replication. The FMDV CRE adopts a stem-loop conformation with an extended duplex stem, supporting a novel 15-17 nucleotide loop that derives stability from base-stacking interactions, with the exact RNA nucleotide sequence of the CRE producing different RNA secondary structures. Here, we show that CRE sequences of FMDVs isolated in Korea from 2010 to 2017 exhibit A and O genotypes. Interestingly, variations in the RNA secondary structure of the Korean FMDVs are consistent with the phylogenetic relationships between these viruses and reveal the specificity of FMDV infections for particular host species. Therefore, we conclude that each genetic clade of Korean FMDV is characterized by a unique functional CRE and that the evolutionary success of new genetic lineages may be associated with the invention of a novel CRE motif. Therefore, we propose that the specific RNA structure of a CRE is an additional criterion for FMDV classification dependent on the host species. These findings will help correctly analyze CRE sequences and indicate the specificity of host species for future FMDV epidemics.

• Korean Journal of Veterinary Service
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• v.42 no.2
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• pp.73-83
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• 2019

Foot-and-Mouth Disease (FMD) is a highly contagious trans-boundary viral disease caused by FMD virus, which causes huge economic losses. FMDV infects cloven hoofed (two-toed) mammals such as cattle, sheep, goats, pigs and various wildlife species. To control the FMDV, it is necessary to understand the life cycle and the pathogenesis of FMDV in host. Especially, the protein-protein interaction between FMDV and host will help to understand the survival cycle of viruses in host cell and establish new therapeutic strategies. However, the computational approach for protein-protein interaction between FMDV and pig hosts have not been applied to studies of the onset mechanism of FMDV. In the present work, we have performed the prediction of the pig's proteins which interact with FMDV based on RNA-Seq data, protein sequence, and structure information. After identifying the virus-host interaction, we looked for meaningful pathways and anticipated changes in the host caused by infection with FMDV. A total of 78 proteins of pig were predicted as interacting with FMDV. The 156 interactions include 94 interactions predicted by sequence-based method and the 62 interactions predicted by structure-based method using domain information. The protein interaction network contained integrin as well as STYK1, VTCN1, IDO1, CDH3, SLA-DQB1, FER, and FGFR2 which were related to the up-regulation of inflammation and the down-regulation of cell adhesion and host defense systems such as macrophage and leukocytes. These results provide clues to the knowledge and mechanism of how FMDV affects the host cell.

• Applied Biological Chemistry
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• v.48 no.4
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• pp.301-310
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• 2005

Foot-and-mouth disease (FMD) is a highly contagious disease of mammals and has a great potential for causing severe economic loss in susceptible cloven-hoofed animals, such as cattle, pigs, sheep, goats and buffalo. FMDV, a member of the Aphthovirus genus in the Picornaviridae family, is a non-enveloped icosahedral virus that contains a positive sense RNA of about 8.2 kb in size. The genome carries one open reading frame consisting of 3 regions: capsid protein coding region P1, replication related protein coding region P2, and RNA-dependent RNA polymerase coding region P3. FMDV infects pharynx epithelial cell in the respiratory tract and viral replication is active in lung epithelial cell. Morbidity is extremely high. A FMD outbreak in Korea in 2002 caused severe economic loss. Although intense research is undergoing to develop appropriate drugs to treat FMDV infection, there is no specific therapeutic for controlling FMDV infection. Moreover, there is an increasing demand for the development of vaccine strategies against FMDV infection in many countries. In this report, more effective prevention strategies against FMDV infection were reviewed.

• Korean Journal of Veterinary Service
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• v.42 no.1
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• pp.25-30
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• 2019

The objective of this study was to assess the possibility of detecting Foot-and-Mouth Disease Virus (FMDV) from the herd-based oral fluids specimens collected by the cotton ropes from pig farms that were found as FMDV nonstructural protein (NSP) antibodies positive. The cotton ropes were applied to detect FMDV in the selected pig farms which NSP antibodies were continuously detected in 2016, including the one pig farm which FMDV antigen were detected at the specimens from the pigsty environment. As the result, FMDV antigen were not detected in the oral fluid specimens collected by the cotton ropes. Theoretically, to detect FMDV antigen from the pigs with NSP antibodies has very low possibility because FMDV antigen disappeared at the time when NSP antibodies were produced by FMDV. Therefore, in order to detect FMDV antigen from the oral fluids using the cotton rope, it would be more effective to be applied to target the FMDV infected pigs rather than the NSP antibodies positive pigs. The collected oral fluids using cotton rope could be useful test specimens to monitor high-density pig populations for FMDV infection. Then, oral fluids sampling using cotton rope will be used for the efficient FMDV surveillance to detect FMDV antigen.

• Journal of Animal Science and Technology
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• v.63 no.6
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• pp.1376-1385
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• 2021

Foot-and-mouth disease, one of the most contagious diseases in cloven-hoofed animals, causes significant economic losses. The pathogenesis of foot-and-mouth disease virus (FMDV) infection is known to differ with age of the animals. In this study, we aimed to reveal the difference in immunological response in the initial stage of FMDV infection between piglets and adult pigs. Peripheral blood mononuclear cells (PBMCs) were isolated from 3 piglets (8 weeks old) and 3 pigs (35 weeks old) that were not vaccinated against FMDV. O-type FMDV (2 × 10² median tissue culture infectious dose) was inoculated into porcine PBMCs and the cells were incubated at 37.0℃ under 5% CO₂ for various time periods (0, 1, 3, 6, 12, 24, and 48 h). The total RNA was obtained from the FMDV-inoculated PBMCs after each time point, and the virus titer was investigated in these RNA samples. Furthermore, dynamics of mRNA expression of the six tested cytokines (interferon [IFN]-α, IFN-γ, interleukin [IL]-6, IL-8, IL-10, and tumor necrosis factor [TNF]-α) in FMDV-inoculated porcine PBMCs were evaluated by time-series analysis to determine the differences, if any, based on the age of the pigs. The PBMCs of piglets contained the highest quantity of FMDV mRNA at 6 hours post-inoculation (hpi), and the PBMCs of pigs had the highest quantity of FMDV mRNA at 3 hpi. The mean cycle threshold-value in the PBMCs steadily decreased after the peak time point in the piglets and pigs (6 and 3 hpi, respectively). The dynamics of mRNA expression of all cytokines except TNF-α showed age-dependent differences in FMDV-inoculated PBMCs. The mRNA expression of most cytokines was more pronounced in the piglets than in the pigs, implying that the immune response against FMDV showed an age-dependent difference in pigs. In conclusion, within 48 hpi, the 8-week-old piglets responded more rapidly and were more sensitive to FMDV infection than the 35-week-old pigs, which could be associated with the difference in the pathogenesis of FMDV infection among the pigs. These results provide valuable insights into the mechanisms underlying the age-dependent differences in immune response in pigs against FMDV infection.

• Korean Journal of Veterinary Service
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• v.35 no.4
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• pp.255-261
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• 2012

Foot and mouth disease (FMD) is highly infectious disease of cloven-hoofed animals, particularly cattle, sheep, pigs and goats. Last outbreak reported in November, 2010 induced the enormous social and economical impacts. Culling of infected animals, movement control, and vaccination are the major control measures of FMD. The aim of this study was to detection foot-and-mouth disease virus (FMDV) in the soil and leachate from modeling burial for pig carcass as measured by real-time reverse transcriptase polymerase chain reaction (RT-PCR). FMDV and Coxsakievirus B1 (CVB1) were detected in soil by week 16 and Coxsakievirus B1 (CVB1) by weeks 12, respectively. FMDV and CVB1 also detected by weeks 8 in the leachate. Results from this study provides an evidence that FMDV could be inactivated for safe of pig carcasses infected with FMDV within 4 month in the carcass burial site.

• Korean Journal of Veterinary Service
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• v.42 no.4
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• pp.297-300
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• 2019

In countries with FMD vaccination, as in Korea, typical clinical signs do not appear, and even in FMD positive cases, it is difficult to isolate the FMDV or obtain whole genome sequence. To overcome this problem, more rapid and simple NGS system is required to control FMD in Korea. FMDV (O/Boeun/ SKR/2017) RNA was extracted and sequenced using Ion Torrent's bench-top sequencer with amplicon panel with optimized bioinformatics pipelines. The whole genome sequencing of raw data generated data of 1,839,864 (mean read length 283 bp) reads comprising a total of 521,641,058 (≥Q20 475,327,721). Compared with FMDV (GenBank accession No. MG983730), the FMDV sequences in this study showed 99.83% nucleotide identity. Further study is needed to identify these differences. In this study, fast and robust methods for benchtop next generation sequencing (NGS) system was developed for analysis of Foot-and-mouth disease virus (FMDV) whole genome sequences.

• Journal of Plant Biotechnology
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• v.31 no.4
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• pp.285-293
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• 2004

FMDV is a viral pathogen that caused foot-and-mouth disease in animals. VP1 is a major capsid protein of FMDV. It is known as one of best materials for the FMDV diagnosis and for the development of protein vaccine. In this study, 633 bp of VP1 gene was modified for the expression of VP1 in plant, based on the VP1 DNA sequence from FMDV taiwan O type and from FMDV isolated vietnam. The. deduced DNA fragment was artificially synthesized using the multiple fragment extension with long-nucleotides. A new plant transgenic vector system, pCAMBIA139011 was constructed on the basis of pBI12l and pCAMBIA1390. Using this vector system and GFP gene or modified VP1 gene, each target gene was introduced into Nicotiana tabacum. The insertion of whole target gene was successfully confirmed in each transgenic plant named GFP-A7 and VP1-4, respectively. The expression level of each gene was estimated by RT-PCR and Real-Time PCR using VP1, GFP specific primers.

• Journal of the Korean Magnetic Resonance Society
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• v.7 no.2
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• pp.89-97
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• 2003

Foot-and-mouth disease virus (FMDV) belongs to the aphthovirus genus within the picornavirus which has a single copy of a positive sense RNA. The translation initiation process of FMDV occurs by a cap-independent mechanism directed by a highly structured element (∼435 nt) termed an internal ribosome entry site (IRES). We have designed and prepared FMDV 4-2 RNA (28nt) by in vitro transcription. The 2D NMR data revealed that FMDV 4-2 IRES domain RNA has a flexible loop and bulge conformation. In further study, we need to make an isotope labeled RNA sample and conduct 3D NMR experiments to completely determine the 3D structure. This study may establish a new drug design strategy to treat foot-and mouth disease.