• BMB Reports
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• v.37 no.2
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• pp.192-198
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• 2004

The hepatitis C virus (HCV) core protein is believed to be one of viral proteins that are capable of preventing virus-infected cell death upon various stimuli. But, the effect of the HCV core protein on apoptosis that is induced by various stimuli is contradictory. We examined the possibility that the HCV core protein affects the ceramide-induced cell death in cells expressing the HCV core protein through the sphingomyelin pathway. Cell death that is induced by $C^2$-ceramide and bacterial sphingomyelinase was analyzed in 293 cells that constitutively expressed the HCV core protein and compared with 293 cells that were stably transfected only with the expression vector. The HCV core protein inhibited the cell death that was induced by these reagents. The protective effects of the HCV core protein on ceramide-induced cell death were reflected by the reduced expression of $p21^{WAF1/Cip1/Sid1}$ and the sustained expression of the Bcl-2 protein in the HCV core-expressing cells with respect to the vector-transfected cells. These results suggest that the HCV core protein in 293 cells plays a role in the modulation of the apoptotic response that is induced by ceramide. Also, the ability of the HCV core protein to suppress apoptosis might have important implications in understanding the pathogenesis of the HCV infection.

• Journal of the Korean Society of Radiology
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• v.82 no.5
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• pp.1274-1280
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• 2021

Acute necrotizing encephalopathy (ANE) is a rare but distinctive type of influenza-associated encephalopathy characterized by symmetric multiple lesions with an invariable thalamic involvement. Although the exact pathogenesis of ANE remains unclear, the most prevalent hypothesis is the "cytokine storm," which results in blood-brain-barrier breakdown. We present the case of a 10-year-old boy with fulminant ANE confirmed with serial MRI studies, including diffusion-weighted imaging and susceptibility-weighted imaging. A comparison of these serial images demonstrated detailed and longitudinal changes in MRI findings during the clinical course corresponding to pathophysiological changes. Our case clarifies the pathogenesis of ANE brain lesions using serial imaging studies and suggests that early immunomodulatory therapy reduces brain damage.

• Journal of Microbiology and Biotechnology
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• v.34 no.2
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• pp.233-239
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• 2024

N6-methyladenosine (m6A) RNA methylation has recently emerged as a significant co-transcriptional modification involved in regulating various RNA functions. It plays a vital function in numerous biological processes. Enzymes referred to as m6A methyltransferases, such as the methyltransferase-like (METTL) 3-METTL14-Wilms tumor 1 (WT1)-associated protein (WTAP) complex, are responsible for adding m6A modifications, while m6A demethylases, including fat mass and obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5), can remove m6A methylation. The functions of m6A-methylated RNA are regulated through the recognition and interaction of m6A reader proteins. Recent research has shown that m6A methylation takes place at multiple sites within hepatitis B virus (HBV) RNAs, and the location of these modifications can differentially impact the HBV infection. The addition of m6A modifications to HBV RNA can influence its stability and translation, thereby affecting viral replication and pathogenesis. Furthermore, HBV infection can also alter the m6A modification pattern of host RNA, indicating the virus's ability to manipulate host cellular processes, including m6A modification. This manipulation aids in establishing chronic infection, promoting liver disease, and contributing to pathogenesis. A comprehensive understanding of the functional roles of m6A modification during HBV infection is crucial for developing innovative approaches to combat HBV-mediated liver disease. In this review, we explore the functions of m6A modification in HBV replication and its impact on the development of liver disease.

• Journal of Veterinary Science
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• v.21 no.3
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• pp.49.1-49.14
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• 2020

Background: Coinfection with avian leukosis virus subgroup J (ALV-J) and reticuloendotheliosis virus (REV) is common in chickens, and the molecular mechanism of the synergistic pathogenic effects of the coinfection is not clear. Exosomes have been identified as new players in the pathogenesis of retroviruses. The different functions of exosomes depend on their cargo components. Objectives: The aim of this study was to investigate the function of co-regulation differentially expressed proteins in exosomes on coinfection of ALV-J and REV. Methods: Here, viral replication in CEF cells infected with ALV-J, REV or both was detected by immunofluorescence microscopy. Then, we analyzed the exosomes isolated from supernatants of chicken embryo fibroblast (CEF) cells single infected and coinfected with ALV-J and REV by mass spectrometry. KEGG pathway enrichment analyzed the co-regulation differentially expressed proteins in exosomes. Next, we silenced and overexpressed tripartite motif containing 62 (TRIM62) to evaluate the effects of TRIM62 on viral replication and the expression levels of NCK-association proteins 1 (NCKAP1) and actin-related 2/3 complex subunit 5 (ARPC5) determined by quantitative reverse transcription polymerase chain reaction. Results: The results showed that coinfection of ALV-J and REV promoted the replication of each other. Thirty proteins, including TRIM62, NCK-association proteins 1 (NCKAP1, also known as Nap125), and Arp2/3-5, ARPC5, were identified. NCKAP1 and ARPC5 were involved in the actin cytoskeleton pathway. TRIM62 negatively regulated viral replication and that the inhibition of REV was more significant than that on ALV-J in CEF cells coinfected with TRIM62. In addition, TRIM62 decreased the expression of NCKAP1 and increased the expression of ARPC5 in coinfected CEF cells. Conclusions: Collectively, our results indicated that coinfection with ALV-J and REV competitively promoted each other's replication, the actin cytoskeleton played an important role in the coinfection mechanism, and TRIM62 regulated the actin cytoskeleton.

• BMB Reports
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• v.51 no.7
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• pp.315-316
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• 2018

Genome engineering with clustered regularly interspaced short palindromic repeats (CRISPR) system can be used as a tool to correct pathological mutations or modulate gene expression levels associated with pathogenesis of human diseases. Owing to well-established local administration methods including intravitreal and subretinal injection, it is relatively easy to administer therapeutic genome engineering machinery to ocular tissues for treating retinal diseases. In this context, we have investigated the potential of in vivo genome engineering as a therapeutic approach in the form of ribonucleoprotein or CRISPR packaged in viral vectors. Major issues in therapeutic application of genome engineering include specificity and efficacy according to types of CRISPR system. In addition to previous platforms based on ribonucleoprotein and CRISPR-associated protein 9 derived from Campylobacter jejuni, we evaluated the therapeutic effects of a CRISPR RNA-guided endonuclease derived from Lachnospiraceae bacterium ND2006 (LbCpf1) in regulating pathological angiogenesis in an animal model of wet-type age-related macular degeneration. LbCpf1 targeting Vegfa or Hif1a effectively disrupted the expression of genes in ocular tissues, resulting in suppression of choroidal neovascularization. It was also notable that there were no significant off-target effects in vivo.

• Journal of Microbiology and Biotechnology
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• v.29 no.11
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• pp.1852-1859
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• 2019

Chikungunya virus (CHIKV) is a single-stranded positive-sense RNA virus, belonging to the genus Alphavirus of the Togaviridae family. It causes multiple symptoms, including headache, fever, severe joint and muscle pain, and arthralgia. Since CHIKV was first isolated in Tanzania in 1952, there have been multiple outbreaks of chikungunya fever. However, its pathogenesis and mechanisms of viral immune evasion have been poorly understood. In addition, the exact roles of individual CHIKV genes on the host innate immune response remain largely unknown. To investigate if CHIKV-encoded genes modulate the type I interferon (IFN) response, each and every CHIKV gene was screened for its effects on the induction of the IFN-β promoter. Here we report that CHIKV nsP2, E2 and E1 strongly suppressed activation of the IFN-β promoter induced by the MDA5/RIG-I receptor signaling pathway, suggesting that nsP2, E2, and E1 are the major antagonists against induction of IFN-β. Delineation of underlying mechanisms of CHIKV-mediated inhibition of the IFN-β pathway may help develop virus-specific therapeutics and vaccines.

• Journal of Marine Bioscience and Biotechnology
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• v.2 no.4
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• pp.209-223
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• 2007

Nature is one of the most important sources of pharmacologically active compounds in the search for drugs against life threatening diseases. Even though plants and terrestrial microorganisms have played as an important source for the new drug candidates from nature, marine organisms such as tunicates, sponges, soft corals, sea horses, sea snakes, marine mollusks, seaweeds, nudibranches, sea slugs and marine microorganisms are increasingly attracting attention in recent years. Marine organisms also have the potential to develop into future drugs against important diseases, such as cancer, a range of bacterial and viral diseases, malaria, and inflammations. Even though the mechanism of action in the molecular level of most metabolites is still unclear, the mechanisms by which they interfere with the pathogenesis of a wide range of diseases have been reported. The knowledge of this is one of the key factors necessary to develop bioactive compounds into medicines. This is due to their structurally unique and pharmacologically active compounds. The potential pharmaceutical, medicinal and research applications of some of these compounds are discussed in hundreds of scientific papers, and are reviewed here.

• Korean Journal of Veterinary Service
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• v.25 no.1
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• pp.87-96
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• 2002

In this study, we wanted to determine if the respirotropic JMK strain of infectious bronchitis virus(IBV), which has a spike glycoprotein gene that is 99% similar to the nephropathogenic Gray strain of IBV, could adapt and cause lesions in the kidney following intracloacal passage in chickens. Two day old specific pathogen free(SPF) cchickens were infected with Gray and JMK strains by the intraocular and cloacal route. Several tissue samples were collected at various times. Viruses were recovered from more tissues and earlier in the infection from chickens infected cloacally than chickens infected intraocularly. Virus was isolated from the kidney of chickens infected with Gray by the intraocular route and JMK by the intracloacal route, but not from chicken given JMK the intraocular route. Histopathologically, interstitial nephritis was observed in Gray infected chickens. However, viral RNA or antigen were not detected in the kidney by in situ hybridization and immunohistochemistry. We further passaged the JMK strain ten times in two day old SPF chickens using cloacal inoculation. We examined the virus titer and histopathological change in the kidney at each passage level. The amount of virus recovered from the kidney was stable throughout this serial passage and the passaged virus did not caused renal damage. Further, virus could not be isolated from the kidney when chickens were infected with the passaged virus by the intraocular route. We conclude that the JMK strain has a strict upper respiratory tract tropism since cloacal passage did not produce nephrotropism or nephropathogenicity.

• Korean Journal of Veterinary Research
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• v.61 no.2
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• pp.12.1-12.9
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• 2021

The mosquito-borne pathogen Zika virus may result in neurological disorders such as Guillain-Barré syndrome and microcephaly. The virus is classified as a member of the Flaviviridae family and its wide spread in multiple continents is a significant threat to public health. So, there is a need to develop animal models to examine the pathogenesis of the disease and to develop vaccines. To examine the clinical profile during Zika virus infection, we infected neonatal and adult wild-type mice (C57BL/6 and Balb/c) and compared the clinical signs of African-lineage strain (MR766) and Asian-lineage strain (PRVABC59, MEX2-81) of Zika virus. Consistent with previous reports, eight-week-old female Balb/c mice infected with these viral strains showed no changes in body weight, survival rate, and neurologic signs, but demonstrated increases in the weights of spleens and hearts. However, one-day-old neonates showed significantly lower survival rate and body weight with the African-lineage strain than the Asian-lineage strain. These results confirmed the pathogenic differences between Zika virus strains. We also evaluated the clinical responses in neonatal and adult mice of different strains. Our findings suggest that these are useful mouse models for characterization of Zika virus for vaccine development.

• Journal of Microbiology and Biotechnology
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• v.31 no.2
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• pp.226-232
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• 2021

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging phlebovirus of the Phenuiviridae family that has been circulating in the following Asian countries: Vietnam, Myanmar, Taiwan, China, Japan, and South Korea. Despite the increasing infection rates and relatively high mortality rate, there is limited information available regarding SFTSV pathogenesis. In addition, there are currently no vaccines or effective antiviral treatments available. Previous reports have shown that SFTSV suppresses the host immune response and its nonstructural proteins (NSs) function as an antagonist of type I interferon (IFN), whose induction is an essential part of the host defense system against viral infections. Given that SFTSV NSs suppress the innate immune response by inhibiting type I IFN, we investigated the mechanism utilized by SFTSV NSs to evade IFNmediated response. Our co-immunoprecipitation data suggest the interactions between NSs and retinoic acid inducible gene-I (RIG-I) or TANK binding kinase 1 (TBK1). Furthermore, confocal analysis indicates the ability of NSs to sequester RIG-I and related downstream molecules in the cytoplasmic structures called inclusion bodies (IBs). NSs are also capable of inhibiting TBK1-interferon regulatory factor 3 (IRF3) interaction, and therefore prevent the phosphorylation and nuclear translocation of IRF3 for the induction of type I IFN. The ability of SFTSV NSs to interact with and sequester TBK1 and IRF3 in IBs demonstrate an effective yet unique method utilized by SFTSV to evade and suppress host immunity.