• Korean Journal of Poultry Science
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• v.48 no.2
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• pp.81-90
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• 2021

Avian influenza viruses (AIVs) must utilize host cellular factors to complete their life cycle, and fragile X mental retardation protein (FMRP) has been reported to be a host factor promoting AIV ribonucleoprotein (vRNP) assembly and exports vRNP from the nucleus to the cytoplasm. The functional role of chicken FMRP translational regulator 1 (cFMR1) as a host factor of AIV is, however, poorly understood. In this study, we targeted the cFMR1 gene in DF1 cells using clustered regularly interspaced short palindromic repeats/Cas9-mediated genome editing to examine the functional role of cFMR1 as a host factor of AIV. We found that cFMR1 stimulated viral gene transcription during early stages of the viruses' life cycle and did not affect viral progeny production and viral polymerase activity in DF1 cells 24 hours post infection. cFMR1 overexpression did not exert significant effects on virus production, compared to the control. Therefore, unlike in mammalian systems (e.g., humans or mice), cFMR1 did not play a pivotal role in AIV but only seemed to stimulate viral proliferation during early stages of the viral life cycle. These results imply that the interplay between host factors and AIV differs between mammals and avian species, and such differences should be considered when developing anti-viral drugs for birds or establishing AIV-resistant bird models.

• Biomolecules & Therapeutics
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• v.7 no.4
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• pp.377-384
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• 1999

Alginates are polysaccharides with gel-forming properties composed of 1,4-linked $\beta$-D-mannuronic acid (M), $\alpha$-L-guluronic acid (G), and alternating (MG) blocks. The M-and the MG-blocks, but not the G-blocks, have been known to be the active components of the alginates in experimental models. In this study, we have examined the ability of high M-alginate to activate immune cells. Alginate induced the macrophage anti-viral activity and the lymphocyte blastogenesis, and enhanced cytotoxicity of natural killer cell. In addition, alginates stimulated the macrophages to induce the production of $H_{2}O_{2}$, whereas alginates had no effect on NO production and suppressed the production of TNF-$\alpha$. These findings suggest that high M-alginate may be modulating various elements of the host immune response.

• Journal of Microbiology and Biotechnology
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• v.30 no.2
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• pp.172-177
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• 2020

Influenza viruses cause respiratory diseases in humans and animals with high morbidity and mortality rates. Conventional anti-influenza drugs are reported to exert side effects and newly emerging viral strains tend to develop resistance to these commonly used agents. Fritillaria thunbergii (FT) is traditionally used as an expectorant for controlling airway inflammatory disorders. Here, we evaluated the therapeutic effects of FT extracts against influenza virus type A (H1N1) infection in vitro, in ovo, and in vivo. In the post-treatment assay, FT extracts showed high CC50 (7,500 ㎍/ml), indicating low toxicity, and exerted moderate antiviral effects compared to oseltamivir (SI 50.6 vs. 222) in vitro. Antiviral activity tests in ovo revealed strong inhibitory effects of both FT extract and oseltamivir against H1N1 replication in embryonated eggs. Notably, at a treatment concentration of 150 mg/kg, only half the group administered oseltamivir survived whereas the FT group showed 100% survival, clearly demonstrating the low toxicity of FT extracts. Consistent with these findings, FT-administered mice showed a higher survival rate with lower body weight reduction relative to the oseltamivir group upon treatment 24 h after viral infection. Our collective results suggest that FT extracts exert antiviral effects against influenza H1N1 virus without inducing toxicity in vitro, in ovo or in vivo, thereby supporting the potential utility of FT extract as a novel candidate therapeutic drug or supplement against influenza.

• Mass Spectrometry Letters
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• v.3 no.4
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• pp.104-107
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• 2012

Mollugin isolated from Rubia cordifolia is known to have anti-inflammatory, anti-cancer, and anti-viral activities. In the present study, a cocktail probe assay and LC-MS/MS were used to investigate the modulating effect of mollugin on cytochrome P450 (CYP) enzymes in male ICR mice. After mollugin was orally administrated to mice at the 20, 40, or 80 mg/kg for 3 days, the activities of CYP in hepatic S-9 fractions were investigated. Unlike the selective inhibitory effect of mollugin on CYP1A2-catalyzed phenacetin O-deethylation in vitro, mollugin only significantly inhibited the activity of CYP2E1-catalyzed chlorzoxazone 6-hydroxylase in vivo. The activities of other CYPs were only slightly altered by mollugin. The results of this study suggest that mollugin might cause herb-drug interactions via the selective inhibition of CYP2E1 in vivo.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.77-77
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• 1995

Human immunodeficiency virus type 1 (HIV-1) contains several nonstructural genes which are required for the viral replication and disease pathogenesis. Among them, tat and nef genes encode an essential transactivator of HIV-1 LTR and a pluripotent protein which seems to be essential for the in vivo but not in vitro viral replication, respectively. We constructed two tat and n of defective HIV-1 and tested for their ability to replicate in several T cells. The defective viruses did not replicate in CD4$\^$+/ T cells, but rescued in the recombinant Jurkat-tat cell which also contains tat gene. The replication of tat and nef defective HIV-1 which expresses chloramphenicol acetyltransferase(CAT) gene was easily detected by a sensitive CAT assay. No revertant was identified during the passages of the mutant viruses for more than two months in Jurkat-tat cells. tat and n of defective HIV-1 could be used instead of wild type viruse for several purposes such as inhibitor screening and development of attenuated AIDS vaccine.

• The Korea Journal of Herbology
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• v.29 no.6
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• pp.63-71
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• 2014

Objectives : Lonicerae japonicae Flos(LJF) has been reported to exhibit anti-oxidant, anti-inflammatory, anti-viral, anti-rheumatoid properties. However, it is still largely unknown whether LJF inhibits the ultraviolet(UV)B-induced oxidative damage in human HaCaT keratinocytes. Therefore in this paper, we investigated the anti-oxidative capacity and protective effect of LJF against UVB-induced oxidative demage in human HaCaT keratinocytes. Methods : To evaluate the anti-oxidative activity of LJF extracts, we measured total phenolic contents, total flavonoid contents, antioxidant capacity, and superoxide scavenging activity. To give an oxidative stress to HaCaT cells, UVB was irradiated with $200mJ/cm^2$ to HaCaT cells. To detect the protective effect of LJF against UVB, we measured cell viability, DNA fragmentation and reactive oxygen species (ROS) production. In addition, we performed high-performance liquid chromatography (HPLC) analysis to find a major component of LJF. Results : LJF contained phenolic and flavonoid contents, and showed the anti-oxidant and superoxide scavenging activity. The UVB-induced oxidative conditions led to the cell death, DNA fragmentation and reactive oxygen species (ROS) production. However, pretreatment with LJF reduced oxidative conditions, including inhibition of cell death, DNA fragmentation and ROS production. In addition, we found out chlorogenic acid as major component of LJF. Conclusions : These results could suggest that LJF contained anti-oxidative contents and exhibited protective effects against UVB on human HaCaT keratinocytes. And the effective compound of LJF which could show protective activities against UVB is chlorogenic acid. Thus, LJF and chlorogenic acid would be useful for the development of drug or cosmetics treating skin troubles.

• Bulletin of the Korean Chemical Society
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• v.34 no.3
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• pp.837-850
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• 2013

Bovine viral diarrhea virus (BVDV), a major pathogen of cattle, is a well-characterized pestivirus which has been used as a good model virus for HCV. The RNA-dependent RNA polymerase (RdRp) plays a key role in the RNA replication process, thus it has been targeted for antivirus drugs. We employed two-dimensional quantitative structure-activity relationship (2D-QSAR) and molecular field analysis (MFA) to identify the molecular substructure requirements, and the particular characteristics resulted in increased inhibitory activity for the known series of compounds to act as effective BVDV inhibitors. The 2D-QSAR study provided the rationale concept for changes in the structure to have more potent analogs focused on the class of arylazoenamines, benzimidazoles, and acridine derivatives with an optimal subset of descriptors, which have significantly contributed to overall anti-BVDV activity. MFA represented the molecular patterns responsible for the actions of antiviral compound at their receptors. We conclude that the polarity and the polarizability of a molecule play a main role in the inhibitory activity of BVDV inhibitors in the QSAR modeling.

• BMB Reports
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• v.31 no.4
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• pp.355-363
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• 1998

MHC unrestricted, antigen nonspecific killing by $CD4^+$ T-cells against virally-infected target cells was induced following cross-linking of CD4 molecules. The cytotoxicity of antibody-activated $CD4^+$ T-cells was abolished by genistein (4',5,7-trihydroxyisoflavone), a protein tyrosine kinase (PTK) inhibitor, but not by H-7, a protein kinase C (PKC) inhibitor. Genisteintreated human or bovine peripheral blood $CD4^+$ T-cells lacked PTK activity and failed to kill virally-infected target cells even after cross-linking of CD4 molecules. The cross-linking of CD4 molecules did not induce effector cell proliferation or the transcription of TNF ${\beta}$. TNF ${\beta}$ synthesis was up-regulated by incubating antibody activated effector cells with bovine herpesvirus type 1 (BHV-1) infected D17 target cells. Anti-TNF ${\beta}$ antibody partially abrogated direct effector cell-mediated antiviral cytotoxicity. On the other hand, this antibody effectively neutralized antiviral activity of effector and target cell culture supernatants against BHV-1 infected D17 cells. The inhibition level of the antiviral activity by the antibody was dependent on effector and target cell ratio. These findings have importance to define the mechanisms of how CD4 cytotoxic cells control viral infection.

• Korean Journal of Microbiology
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• v.52 no.4
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• pp.482-486
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• 2016

Inonotus obliquus is a medicinal mushroom with a variety of biological activities. It has reported to have strong anti-cancer, antioxidant and anti-inflammatory properties. EBV+ gastric carcinoma is one of the most common EBV-associated cancers that were caused by latent EBV infection. In this study, we investigated the anti-cancer effects of ethanol extract of I. obliquus using in vivo xenograft animal models implanted with EBV+ human gastric carcinoma (SNU719). We also explored the molecular mechanisms responsible for its anti-cancer activity. The result indicated that the extract of I. obliquus had an anti-cancer effect in in vivo xenograft mice with EBV+ gastric carcinoma (SNU719). Extract of I. obliquus also showed a great effect on inducing the expression of p53, p21 and Bax in tumor tissue derived from EBV+ human gastric carcinoma, and these were correlated with increased expressions of the cleaved forms of caspase-9 and Parp. Also, I. obliquus attenuated the expression of viral proteins, BZLF-1 and LMP-2 in tumor tissue from EBV+ human gastric carcinoma.

• Nutrition Research and Practice
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• v.10 no.1
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• pp.3-10
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• 2016

BACKGROUND/OBJECTIVES: Oligonol, mainly found in lychee fruit, is an antioxidant polyphenolic compound which has been shown to have anti-inflammatory and anti-cancer properties. The detailed mechanisms by which oligonol may act as an anti-aging molecule have not been determined. MATERIALS/METHODS: In this study, we evaluated the ability of oligonol to modulate sirtuin (SIRT) expression in human lung epithelial (A549) cells. Oligonol was added to A549 cells and reactive oxygen species production, mitochondrial superoxide formation, and p21 protein levels were measured. Signaling pathways activated upon oligonol treatment were also determined by western blotting. Furthermore, the anti-aging effect of oligonol was evaluated ex vivo in mouse splenocytes and in vivo in Caenorhabditis elegans. RESULTS: Oligonol specifically induced the expression of SIRT1, whose activity is linked to gene expression, metabolic control, and healthy aging. In response to influenza virus infection of A549 cells, oligonol treatment significantly up-regulated SIRT1 expression and down-regulated viral hemagglutinin expression. Oligonol treatment also resulted in the activation of autophagy pathways and the phosphorylation of AMP-activated protein kinase (AMPK). Furthermore, oligonol-treated spleen lymphocytes from old mice showed increased cell proliferation, and mRNA levels of SIRT1 in the lungs of old mice were significantly lower than those in the lungs of young mice. Additionally, in vivo lethality assay revealed that oligonol extended the lifespan of C. elegans infected with lethal Vibrio cholerae. CONCLUSIONS: These data demonstrated that oligonol may act as an anti-aging molecule by modulating SIRT1/autophagy/AMPK pathways.