• Title/Summary/Keyword: zoonosis

Search Result 211, Processing Time 0.023 seconds

Zika Virus-Encoded NS2A and NS4A Strongly Downregulate NF-κB Promoter Activity

  • Lee, Jeong Yoon;Nguyen, Thi Thuy Ngan;Myoung, Jinjong
    • Journal of Microbiology and Biotechnology
    • /
    • v.30 no.11
    • /
    • pp.1651-1658
    • /
    • 2020
  • Since Zika virus (ZIKV) was first detected in Uganda in 1947, serious outbreaks have occurred globally in Yap Island, French Polynesia and Brazil. Even though the number of infections and spread of ZIKV have risen sharply, the pathogenesis and replication mechanisms of ZIKV have not been well studied. ZIKV, a recently highlighted Flavivirus, is a mosquito-borne emerging virus causing microcephaly and the Guillain-Barre syndrome in fetuses and adults, respectively. ZIKV polyprotein consists of three structural proteins named C, prM and E and seven nonstructural proteins named NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5 in an 11-kb single-stranded positive sense RNA genome. The function of individual ZIKV genes on the host innate immune response has barely been studied. In this study, we investigated the modulations of the NF-κB promoter activity induced by the MDA5/RIG-I signaling pathway. According to our results, two nonstructural proteins, NS2A and NS4A, dramatically suppressed the NF-κB promoter activity by inhibiting signaling factors involved in the MDA5/RIG-I signaling pathway. Interestingly, NS2A suppressed all components of MDA5/RIG-I signaling pathway, but NS4A inhibited most signaling molecules, except IKKε and IRF3-5D. In addition, both NS2A and NS4A downregulated MDA5-induced NF-κB promoter activity in a dosedependent manner. Taken together, our results suggest that NS2A and NS4A signifcantly antagonize MDA5/RIG-I-mediated NF-κB production, and these proteins seem to be controlled by different mechanisms. This study could help understand the mechanisms of how ZIKV controls innate immune responses and may also assist in the development of ZIKV-specific therapeutics.

Middle East Respiratory Syndrome Coronavirus-Encoded Accessory Proteins Impair MDA5-and TBK1-Mediated Activation of NF-κB

  • Lee, Jeong Yoon;Bae, Sojung;Myoung, Jinjong
    • Journal of Microbiology and Biotechnology
    • /
    • v.29 no.8
    • /
    • pp.1316-1323
    • /
    • 2019
  • Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging coronavirus which is zoonotic from bats and camels. Its infection in humans can be fatal especially in patients with preexisting conditions due to smoking and chronic obstructive pulmonary disease (COPD). Among the 25 proteins encoded by MERS-CoV, 5 accessory proteins seem to be involved in viral evasion of the host immune responses. Here we report that ORF4a, ORF4b, and ORF8b proteins, alone or in combination, effectively antagonize nuclear factor kappa B ($NF-{\kappa}B$) activation. Interestingly, the inhibition of $NF-{\kappa}B$ by MERS-CoV accessory proteins was mostly at the level of pattern recognition receptors: melanoma differentiation-associated gene 5 (MDA5). ORF4a and ORF4b additively inhibit MDA5-mediated activation of $NF-{\kappa}B$ while that of retinoic acid-inducible gene 1 (RIG-I) is largely not perturbed. Of note, ORF8b was found to be a novel antagonist of MDA5-mediated $NF-{\kappa}B$ activation. In addition, ORF8b also strongly inhibits Tank-binding kinase 1 (TBK1)-mediated induction of $NF-{\kappa}B$ signaling. Taken together, MERS-CoV accessory proteins are involved in viral escape of $NF-{\kappa}B$-mediated antiviral immune responses.

Chikungunya Virus nsP2 Impairs MDA5/RIG-I-Mediated Induction of NF-κB Promoter Activation: A Potential Target for Virus-Specific Therapeutics

  • Bae, Sojung;Lee, Jeong Yoon;Myoung, Jinjong
    • Journal of Microbiology and Biotechnology
    • /
    • v.30 no.12
    • /
    • pp.1801-1809
    • /
    • 2020
  • Chikungunya virus (CHIKV) was first identified in 1952 as a causative agent of outbreaks. CHIKV is transmitted by two mosquito species, Aedes aegypti and A. albopictus. Symptoms after CHIKV infection in human are typically fever and joint pain, but can also include headache, muscle pain, joint swelling, polyarthralgia, and rash. CHIKV is an enveloped single-stranded, positive-sense RNA virus with a diameter of approximately 70 nm. The pathogenesis of CHIKV infection and the mechanism by which the virus evades the innate immune system remain poorly understood. Moreover, little is known about the roles of CHIKV-encoded genes in the viral evasion of host immune responses, especially type I interferon (IFN) responses. Therefore, in the present study, we screened CHIKV-encoded genes for their regulatory effect on the activation of nuclear factor kappa B (NF-κB), a critical transcription factor for the optimal activation of IFN-β. Among others, non-structural protein 2 (nsP2) strongly inhibited melanoma differentiation-associated protein 5 (MDA5)-mediated induction of the NF-κB pathway in a dose-dependent manner. Elucidation of the detailed mechanisms of nsP2-mediated inhibition of the MDA5/RIG-I signaling pathway is anticipated to contribute to the development of virus-specific therapeutics against CHIKV infection.

Subcutaneous Streptococcus dysgalactiae GAPDH vaccine in mice induces a proficient innate immune response

  • Ran An;Yongli Guo;Mingchun Gao;Junwei Wang
    • Journal of Veterinary Science
    • /
    • v.24 no.5
    • /
    • pp.72.1-72.16
    • /
    • 2023
  • Background: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) on the surface of Streptococcus dysgalactiae, coded with gapC, is a glycolytic enzyme that was reported to be a moonlighting protein and virulence factor. Objective: This study assessed GAPDH as a potential immunization candidate protein to prevent streptococcus infections. Methods: Mice were vaccinated subcutaneously with recombinant GAPDH and challenged with S. dysgalactiae in vivo. They were then evaluated using histological methods. rGAPDH of mouse bone marrow-derived dendritic cells (BMDCs) was evaluated using immunoblotting, reverse transcription quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay methods. Results: Vaccination with rGAPDH improved the survival rates and decreased the bacterial burdens in the mammary glands compared to the control group. The mechanism by which rGAPDH vaccination protects against S. dysgalactiae was investigated. In vitro experiments showed that rGAPDH boosted the generation of interleukin-10 and tumor necrosis factor-α. Treatment of BMDCs with TAK-242, a toll-like receptor 4 inhibitor, or C29, a toll-like receptor 2 inhibitor, reduced cytokines substantially, suggesting that rGAPDH may be a potential ligand for both TLR2 and TLR4. Subsequent investigations showed that rGAPDH may activate the phosphorylation of MAPKs and nuclear factor-κB. Conclusions: GAPDH is a promising immunization candidate protein for targeting virulence and enhancing immune-mediated protection. Further investigations are warranted to understand the mechanisms underlying the activation of BMDCs by rGAPDH in a TLR2- and TLR4-dependent manner and the regulation of inflammatory cytokines contributing to mastitis pathogenesis.

Study of the Surface Acoustic Wave Biosensors for Detection of the Immunoglobulin G (자가면역글로불린 G 측정을 위한 표면탄성파 바이오센서에 대한 연구)

  • Kim, Gi-Beum;Cheong, Woo-Suk;Park, Young-Ran;Kim, Shang-Jin;Kim, Seong-Jong;Kang, Hyung-Sub;Kim, Jin-Shang;Hong, Chul-Un
    • Korean Chemical Engineering Research
    • /
    • v.49 no.2
    • /
    • pp.224-229
    • /
    • 2011
  • In this study, we have developed shear horizontal(SH) surface acoustic wave(SAW) sensors for the detection of immunoglobulin G(IgG) on the gold coated delay line of SH-SAW devices. As the result of the experiment, we could uniformly immobilize anti-MIgG(mouse IgG) conjugate on the surface of gold. When displaying results of immobilization on the surface of gold using G-anti MIgG conjugate and blocking buffer in frequency shift, G-anti MIgG conjugate showed frequency shift of 75.1 kHz in the initial frequency, and blocking buffer showed frequency shift of 215.7 kHz. When various concentrations of MIgG was added in 100MHz type sensor, the sensor showed 46.3, 127.45, 161.21 and 262.39 kHz frequency shift at 25, 50, 75 and 100 ${\mu}g$ MIgG concentration, respectively.

Study on the Fluid Dynamics Modeling in Artificial Lung Assist Device (인공 폐 보조장치 내에서의 유체 유동 모델링에 대한 연구)

  • Kim, Gi-Beum;Park, Young-Ran;Kim, Shang-Jin;Hong, Chul-Un;Kang, Hyung-Sub;Kim, Jin-Shang;Kim, Seong-Jong;Kim, Min-Ho
    • Korean Chemical Engineering Research
    • /
    • v.49 no.2
    • /
    • pp.230-237
    • /
    • 2011
  • In this study, the characteristic of fluid flow in the new type lung assist devices has been established using computational fluid dynamics(CFD). For the modeling, the hollow fiber was ignored, and vertical types and tangential types were used for the model. Which was to analyze the flow characteristics of the fluid flow model when there exists 1 and 2 input/output ports, and when the input/output ports is located at the center of the cylinder and at the tangential direction with the cylinder wall. The modeling results showed that it was possible to eliminate no-flow region(stagnant layer) as shown in the vertical type when an inlet and an outlet were installed on the tangential direction of the cylinder as shown in the tangential type. Also, in the tangential type, vortex-type flow appeared as dominant, and it showed a complicated flow not deviated to one side. When the number of input/output was two, there was no deviated flow, and complicated flows were generated all across the tube. From the test result, it was found that input/output of flow was tangential type and complicated flows with no stagnant layer would be generated when there are two inputs/outputs, respectively.

Modeling of Hemodynamics in Stenosed Artery (협착 동맥혈관의 혈류유동 모델링)

  • Kim, Seong-Jong;Park, Young-Ran;Kim, Shagn-Jin;Kang, Hyung-Sub;Kim, Jin-Shang;Oh, Sung-Hoon;Kang, Sung-Jun;Kim, Gi-Beum
    • Journal of the Korea Academia-Industrial cooperation Society
    • /
    • v.13 no.5
    • /
    • pp.2285-2290
    • /
    • 2012
  • This study is about atherosclerosis which occupies the highest rate in many diseases people have and we have studied about atherosclerosis for abdominal aorta. Atherosclerosis is the phenomenon which blood vessel gets narrower, harder and thicker due to the stenosis of colesterol in blood vessel. If it becomes worse, arteries will be hard and blood can't flow smoothly, and even it can reach to death. In this study, the geometric models of the considered stenotic blood flow are two different types of constriction of cross-sectional area of blood vessel; 20 and 45% of constriction in each elastic wall and rigid wall. We have modeled by using finite element method to observe the changes of velocity and pressure. In case of the diameter of blood vessel decreased 45% in elastic wall model, the values of velocity and pressure were higher than the case of 20% and in case of the diameter of blood vessel decreased 45% in rigid wall model, the values of velocity and pressure were higher than the case of 20%. In cases of elastic wall models of the diameters of blood vessels decreased each of 20% and 45%, recirculation zones appeared. This results show understanding of hemodynamic properties depending on stenosed blood vessels.

Hepatitis E Virus Papain-Like Cysteine Protease Inhibits Type I Interferon Induction by Down-Regulating Melanoma Differentiation-Associated Gene 5

  • Kim, Eunha;Myoung, Jinjong
    • Journal of Microbiology and Biotechnology
    • /
    • v.28 no.11
    • /
    • pp.1908-1915
    • /
    • 2018
  • Upon viral infection, the host cell recognizes the invasion through a number of pattern recognition receptors. Melanoma differentiation associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I) recognize RNA molecules derived from invading viruses, activating down-stream signaling cascades, culminating in the induction of the type I interferon. On the other hand, viruses have evolved to evade type I interferon-mediated inhibition. Hepatitis E virus has been shown to encode a few antagonists of type I interferon and it is not surprising that viruses encode multiple mechanisms of viral evasion. In the present study, we demonstrated that HEV PCP strongly down-regulates MDA5-mediated activation of interferon ${\beta}$ induction in a dose-dependent manner. Interestingly, MDA5 protein expression was almost completely abolished. In addition, polyinosinic polycytidylic acid (poly(I:C))- and Sendai virus-mediated activation of type I interferon responses were similarly abrogated in the presence of HEV PCP. Furthermore, HEV PCP down-regulates several molecules that play critical roles in the induction of type I IFN expression. Taken together, these data collectively suggest that HEV-encoded PCP is a strong antagonist of type I interferon.

Detection of Ehrlichia chaffeensis pathogen from deer in Korea

  • Lee, Mi-Jin;Li, Ying-Hua;Yu, Do-Hyeon;Lee, Jong-Hyun;Yoon, Ji-Seon;Song, Hee-Jong;Chae, Joon-Seok;Park, Jin-Ho
    • Korean Journal of Veterinary Service
    • /
    • v.31 no.2
    • /
    • pp.187-193
    • /
    • 2008
  • Ehrlichia chaffeensis infects human and animals, and causes human monocytotropic ehrlichiosis (HME). It is emerging as a tick-borne zoonosis of concern. Although deer are important natural reservoir hosts of E chaffeensis, few surveys of deer in Korea for E chaffeensis have been conducted. Therefore, we conducted this study to confirm the occurrence of E chaffeensis in deer. To accomplish this study, we collected blood from total 27 deer and then polymerase chain reaction (PCR) and 16S rRNA sequence analyse to evaluate the samples for the presence of E chaffeensis. The results of this study indicated that 9 (33%) of the deer were infected with E chaffeensis. This is the first study to demonstrate that deer in Korea are infected with E chaffeensis, which indicates that they can act as a natural reservoir host for E chaffeensis.