Infectious disease research and vaccine development using animal BSL-3 facility

( Dongseob Tark ) 대한인수공통전염병학회 2017 창립총회 및 학술대회 초록집 Vol.2017 No.1

Despite remarkable advances in medical science during the 20th century, infectious diseases remain leading causes of death worldwide for reason such as emergence of new infectious diseases, re-emergence of old infectious diseases, and persistence of endemic diseases. Emerging diseases include outbreaks of unknown diseases or known diseases whose incidence in humans has significantly increased in the past two decades. Re-emerging diseases are known diseases that have reappeared after a significant decline in incidence. There are many infectious diseases that continue to be significant global events and the emergence and re-emergence of pathogens can be threatening the health throughout the 21st century. A large majority of these diseases are occurred by zoonotic microbes, such as HIV, avian influenza, SARS, Ebola, West Nile, Hantavirus, hepatitis E, and many others. Particularly, in South Korea, Middle East respiratory syndrome coronavirus (MERS-CoV) infection outbreak was reported in 2015. A total of 186 MERS-CoV cases, including 36 deaths, have been associated with the outbreak in the country. According to Korea economy research institute report, South Korea`s central bank cut interest rates to stem the economic fallout, and national economy was damaged with US $20 billion from the outbreak. For the research of emerging zoonotic diseases, air-borne disease, arthropod-borne diseases, and food- and water-borne diseases, it is regulated that national biosafety guidelines have been established that promote safe microbiological practices and safety standards to prevent infections disease acquired from laboratory and laboratory animals. Therefore, facilities that licensed animal biosafety level 3 (ABSL-3) or biosafety level 3 (BSL-3) are essential for the infectious disease research. Recently, Korea Zoonosis Research Institute was launched in 2015, and the facilities of BSL-3 and ABSL-3 are certificating by government office. In this paper, I am going to introduce the facility to give attention of international collaboration in the research filed. Regulations in South Korea require guidelines for many zoonotic pathogens or high-pathogenic agents of animal disease to use ABSL-3 or BSL-3 facilities. Many additional issues should be considered in designing and managing large animal-containment facilities. Particularly, technical knowledges and a great amount of budget are essential for the facilities. Most researchers have explained that studies with zoonotic pathogens using ABSL-3 or BSL-3 can be safely conducted after completing numerous studies over many years. For that, national support and policy from the government of each country are essential to solve global public health issues. We have to emphasize that there are public health benefits when the prevalence of zoonotic pathogens such as FMD, MERS, and AI are reduced, leading to reductions in human infection and associated economic costs.

Control of type O foot-and-mouth disease by vaccination in Korea, 2014–2015

박종현,Dongseob Tark,Kwang-Nyeong Lee,천지은,Hyang-Sim Lee,Young-Joon Ko,Soo-Jeong Kye,Yong-Joo Kim,Jae-Ku Oem,유소윤,Sung-Bin Lim,이서용,최주형,고미경,유수화,이명헌,김병한 대한수의학회 2018 Journal of Veterinary Science Vol.19 No.2

On December 3, 2014, a type O foot-and-mouth disease (FMD) outbreak began in Korea. Although vaccinations were administered, FMDcases increased steadily for five months, and reached 185 cases by April 2015. Most of the affected animals were pigs, which are vulnerableto vaccination. The FMD virus belonged to the South-East Asia (SEA) topotype that had been observed three times in Korea between April2010 and July 2014. However, the FMD virus isolated in December 2014 had a unique feature; that is, partial deletion of the 5´ non-codingregion, a deletion not seen in previous SEA topotype isolates identified in Korea. We conclude that this outbreak included the introductionof a new FMD strain to Korea, and that Korea was now affected by genetically similar FMD virus strains that are related to those fromneighboring countries.

Development of monoclonal antibody capture ELISA for the detection of antibodies against transmissible gastroenteritis virus

Oh, Yeonsu,Tark, Dongseob The Korean Society of Veterinary Service 2019 韓國家畜衛生學會誌 Vol.42 No.1

Transmissible gastroenteritis (TGE) is a disease confined to pigs of all ages, and can be a significant cause of economic loss in breeding herds, primarily because of the very high piglet mortality. The causative agent is a coronavirus, an enveloped positive strand RNA virus and closely related but non-enteropathogenic porcine respiratory coronavirus (PRCV). Although the TGEV has declined with its innocent relative, PRCV, further genome changes could not be excluded. Therefore, the herd-level immunity against this virus is important for the prevention of disease and should be carefully monitored. The aim of this study is to develop monoclonal antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) which can rapidly and accurately determine a large numbers of serum samples for surveillance purpose, and to compare the ELISA with a TGEV-specific serum neutralization test. The MAC-ELISA was sufficiently achieved, and the comparison with the virus-specific serum neutralization assays for 713 sera from pig farms showed a high correlation ($r^2=0.812$, P<0.001). The specificity and sensitivity of MAC-ELISA for the serum neutralization test 91.9% and 91.6%, respectively, which means that the antibody detected by the MAC-ELISA could be said to be protective antibodies. In conclusion, the developed MAC-ELISA would be very helpful in evaluating protective antibodies against TGEV.

Sepsis Caused by <i>Streptococcus suis</i> Serotype 2 in a Eurasian River Otter (<i>Lutra lutra</i>) in the Republic of Korea

Oh, Yeonsu,Tark, Dongseob,Moon, Sung-Hyun,Han, Jae-Ik,Kim, Won-Il,Cho, Ho-Seong Wildlife Disease Association 2018 JOURNAL OF WILDLIFE DISEASES Vol.54 No.4

Decadal analysis of livestock tuberculosis in Korea (2013∼2022): Epidemiological patterns and trends

( Yeonsu Oh ),( Dongseob Tark ),( Gwang-seon Ryoo ),( Dae-sung Yoo ),( Woo H. Kim ),( Won-il Kim ),( Choi-kyu Park ),( Won-keun Kim ),( Ho-seong Cho ) 한국동물위생학회 2023 韓國家畜衛生學會誌 Vol.46 No.4

This study provides a comprehensive analysis of the epidemiological trends and challenges in managing tuberculosis (TB) in livestock in Korea from 2013 to 2022. Tuberculosis, caused by the Mycobacterium tuberculosis complex, is a significant zoonotic disease affecting cattle, deer, and other domesticated animals. Despite the initiation of a test-and-slaughter eradication policy in 1964, TB has continued to persist in Korean livestock, particularly in cattle and deer. This study used data from the Korea Animal Health Integrated System and provincial animal health laboratories to analyze TB incidence in various livestock including different cattle breeds and deer species. The results from 2013 to 2022 showed a peak in TB cases in 2019 with a subsequent decline by 2022. The study highlighted a significant incidence of TB in Korean native cattle and the need for amore inclusive approach towards TB testing and control in different cattle breeds. Additionally, the study underscored the importance of addressing TB in other animals such as goats, wildlife, and companion animals for a holistic approach to TB eradication in Korea. The findings suggest that while the test-and-slaughter strategy has been historically effective, there is a need for adaptation to the current challenges, and learning from successful eradiation stories on other countries like Australia. A collaborative effort involving an expanded surveillance system, active private sector participation, and robust government support essential for the efficient eradication of TB in livestock in Korea.

Sustained SARS-CoV-2 antibody response in domestic pets: Insights from a longitudinal study

( Yeonsu Oh ),( Dongseob Tark ),( Choi-kyu Park ),( Ho-seong Cho ) 한국동물위생학회 2023 韓國家畜衛生學會誌 Vol.46 No.4

The COVID-19 pandemic, triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has not only impacted human health on a global scale but also raised concerns about the vulnerability of a wide array of animals that are in close contact with humans. Particularly, the potential for infection and the subsequent immune response in domestic pets such as dogs and cats remain largely unexplored under natural living conditions. In this study, we have undertaken the task of detecting and tracking the presence of antibodies against SARS-CoV-2 in a small cohort of household pets-specifically, two dogs and two cats. Employing techniques such as the indirect ELISA and plaque reduction neutralization tests, we observed that the neutralizing antibodies against SARS-CoV-2 in these animals were maintained for a duration of up to six months following their initial positive test result. This duration mirrors the antibody response documented in human cases of COVID-19, suggesting a comparable post-infection immune response timeline between humans and these domestic animals.

Development of monoclonal antibody capture ELISA for the detection of antibodies against transmissible gastroenteritis virus

Yeonsu Oh,Dongseob Tark 한국동물위생학회 2019 韓國家畜衛生學會誌 Vol.42 No.1

Transmissible gastroenteritis (TGE) is a disease confined to pigs of all ages, and can be a significant cause of economic loss in breeding herds, primarily because of the very high piglet mortality. The caus-ative agent is a coronavirus, an enveloped positive strand RNA virus and closely related but non-enter-opathogenic porcine respiratory coronavirus (PRCV). Although the TGEV has declined with its innocent relative, PRCV, further genome changes could not be excluded. Therefore, the herd-level immunity against this virus is important for the prevention of disease and should be carefully monitored. The aim of this study is to develop monoclonal antibody capture enzyme-linked immunosorbent assay (MAC- ELISA) which can rapidly and accurately determine a large numbers of serum samples for surveillance purpose, and to compare the ELISA with a TGEV-specific serum neutralization test. The MAC-ELISA was sufficiently achieved, and the comparison with the virus-specific serum neutralization assays for 713 sera from pig farms showed a high correlation (r2=0.812, P<0.001). The specificity and sensitivity of MAC-ELISA for the serum neutralization test 91.9% and 91.6%, respectively, which means that the an-tibody detected by the MAC-ELISA could be said to be protective antibodies. In conclusion, the devel-oped MAC-ELISA would be very helpful in evaluating protective antibodies against TGEV.

Whole genome sequencing of foot-and-mouth disease virus using benchtop next generation sequencing (NGS) system

Sung-Hyun Moon,오연수,Dongseob Tark,조호성 한국동물위생학회 2019 韓國家畜衛生學會誌 Vol.42 No.4

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 show-ed 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.

Determination of optimal age for single vaccination of growing pigs with foot-and-mouth disease bivalent vaccine in South Korea

KIM, Ah-Young,TARK, Dongseob,KIM, Hyejin,KIM, Jae-Seok,LEE, Jung-Min,KWON, Minhee,BAE, Soohyun,KIM, Byounghan,KO, Young-Joon JAPANESE SOCIETY OF VETERINARY SCIENCE 2017 The Journal of veterinary medical science Vol.79 No.11

<P>In South Korea, pigs were vaccinated once between 8 and 12 weeks of age because of the injection-site granulomas. Therefore this study was performed to determine the optimal age for single vaccination of growing pigs with the currently used type O FMD vaccine. With 498 pigs divided into four groups, seroprevalence of the antibody was analyzed with enzyme-linked immunosorbent assay. Although double vaccination is necessary to completely protect growing pigs from FMD virus infection with the current vaccine, the age of 8 weeks can be considered as the optimal age for piglet vaccination if the booster injection is unavailable.</P>

Hepatitis C Virus Nonstructural Protein 5A Interacts with Immunomodulatory Kinase IKKε to Negatively Regulate Innate Antiviral Immunity

Sang Min Kang,박지영,한희정,송병민,Dongseob Tark,Byeongsun Choi,Soon B. Hwang 한국분자세포생물학회 2022 Molecules and cells Vol.45 No.10

Hepatitis C virus (HCV) infection can lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV employs diverse strategies to evade host antiviral innate immune responses to mediate a persistent infection. In the present study, we show that nonstructural protein 5A (NS5A) interacts with an NF-κB inhibitor immunomodulatory kinase, IKKε, and subsequently downregulats beta interferon (IFN-β) promoter activity. We further demonstrate that NS5A inhibits DDX3-mediated IKKε and interferon regulatory factor 3 (IRF3) phosphorylation. We also note that hyperphosphorylation of NS5A mediats protein interplay between NS5A and IKKε, thereby contributing to NS5A-mediated modulation of IFN-β signaling. Lastly, NS5A inhibits IKKε-dependent p65 phosphorylation and NF-κB activation. Based on these findings, we propose NS5A as a novel regulator of IFN signaling events, specifically by inhibiting IKKε downstream signaling cascades through its interaction with IKKε. Taken together, these data suggest an additional mechanistic means by which HCV modulates host antiviral innate immune responses to promote persistent viral infection.