Journal of Microbiology

Journal Article

Roles of human apolipoprotein E in the infectivity and replication of hepatitis C virus genotype 2a: Bo-Kyoung Jung , Hye-Ran Kim , Gyu-Nam Park , Guangxiang Luo , Kyung-Soo Chang; J. Microbiol. 2016;54(6):451-458. Published online May 27, 2016; DOI: https://doi.org/10.1007/s12275-016-6099-3

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Hepatitis C virus (HCV) infection is associated with lipoproteins, and apolipoprotein E (apoE) plays an essential role in infectious HCV particles. Although the role of apoE in HCV infection is well known, its role in the replication of HCV remains unclear. The aims of this study were to determine the role of apoE in the RNA replication of major HCV genotypes 1b and 2a, and to determine whether this role is HCVgenotype- dependent using HCV genotype 1b replicon cells and HCV genotype 2a producing (HP) cells. HCV infection was blocked in Huh7.5 cells treated with low-density lipoproteins, very low-density lipoproteins, or apoE3. An apoE3- specific monoclonal antibody also efficiently neutralized HCV infectivity, and HCV infection was dramatically suppressed by the knockdown of apoE expression with an apoE-specific small interfering RNA, suggesting a requirement for apoE in infectious HCV particles. HCV RNA replication was not affected in HP cells treated with each apoE isoform or transfected with apoE-specific siRNAs. However, the knockdown of apoE expression suppressed RNA replication of HCV genotype 1b. The siRNA-mediated knockdown of apoE, apoA1, and apoB expression also suppressed the RNA replication of HCV genotype 1b, but not that of HCV genotype 2a. Taken together, these findings indicate that apoE plays an important role in HCV genotype 2a infection and in HCV genotype 1b RNA replication, but not in the replication of HCV genotype 2a. These results provide important information for the future development of HCV-genotypespecific anti-HCV agents.

Citations

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The Role of ApoE in HCV Infection and Comorbidity
Yue Gong, Wei Cun
International Journal of Molecular Sciences.2019; 20(8): 2037. CrossRef
How Have Retrovirus Pseudotypes Contributed to Our Understanding of Viral Entry?
Barnabas King, Alexander W Tarr
Future Virology.2017; 12(10): 569. CrossRef

Research Support, Non-U.S. Gov't

Anti-tumor effect of Cordyceps militaris in HCV-infected human hepatocarcinoma 7.5 cells: Seulki Lee , Hwan Hee Lee , Jisung Kim , Joohee Jung , Aree Moon , Choon-Sik Jeong , Hyojeung Kang , Hyosun Cho; J. Microbiol. 2015;53(7):468-474. Published online June 27, 2015; DOI: https://doi.org/10.1007/s12275-015-5198-x

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Abstract

Cordyceps extract has been reported to have various pharmacological activities including an anti-cancer effect. We investigated the inhibitory effect of Cordyceps militaris on hepatitis C virus-infected human hepatocarcinoma 7.5 cells (J6/JFH1-huh 7.5 cells). The huh7.5 cells with or without HCV infection were treated with various concentrations of ethanol extract of Cordyceps militaris (CME) for 48 h and the cytotoxicity was measured by CCK-8 assay. Both J6/JFH1- huh7.5 cells and huh7.5 cells were highly susceptible to CME. To examine the molecular mechanisms of the inhibitory effect on huh7.5 cells, the effect of CME on cell apoptosis was measured using flow cytometry and the expressions of p53, Bim, Bax, PARP, (cleaved) caspase-9, and (cleaved) caspase- 3 in huh 7.5 cells were detected by western blot assays. CME significantly increased early apoptosis and up-regulated the expression of Bim, Bax, cleaved PARP, cleaved caspase 9 and cleaved caspase-3. We also found the decrease of HCV Core or NS3 protein by CME in HCV-infected huh 7.5 cells.

Citations

Citations to this article as recorded by

Visualized Nucleic Acid Hybridization Lateral Flow Strip Integrating with Microneedle for the Point-of-Care Authentication of Ophiocordyceps sinensis
Haibin Liu, Xinyue Wang, Hang Tian, Yi Yuan, Jing Wang, Yani Cheng, Linyao Sun, Hongshuo Chen, Xiaoming Song
International Journal of Molecular Sciences.2024; 25(24): 13599. CrossRef
Novel formulation development from Ophiocordyceps sinensis (Berk.) for management of high-altitude maladies
Rakhee, Jigni Mishra, Renu Bala Yadav, D. K. Meena, Rajesh Arora, R. K. Sharma, Kshipra Misra
3 Biotech.2021;[Epub] CrossRef
A new nucleoside and two new pyrrole alkaloid derivatives from Cordyceps militaris
Yafu Xue, Leilei Wu, Yulian Ding, Xinming Cui, Zhuzhen Han, Hong Xu
Natural Product Research.2020; 34(3): 341. CrossRef
Antitumor and Anti-Invasive Effect of Apigenin on Human Breast Carcinoma through Suppression of IL-6 Expression
Hwan Hee Lee, Joohee Jung, Aree Moon, Hyojeung Kang, Hyosun Cho
International Journal of Molecular Sciences.2019; 20(13): 3143. CrossRef
Cytokine-Modulated Natural Killer Cells Differentially Regulate the Activity of the Hepatitis C Virus
Yoo Cho, Hwan Lee, Hyojeung Kang, Hyosun Cho
International Journal of Molecular Sciences.2018; 19(9): 2771. CrossRef
The genus Cordyceps : An extensive review of its traditional uses, phytochemistry and pharmacology
Opeyemi Joshua Olatunji, Jian Tang, Adesola Tola, Florence Auberon, Omolara Oluwaniyi, Zhen Ouyang
Fitoterapia.2018; 129: 293. CrossRef
Systems Pharmacology-based strategy to screen new adjuvant for hepatitis B vaccine from Traditional Chinese Medicine Ophiocordyceps sinensis
Jingbo Wang, Rui Liu, Baoxiu Liu, Yan Yang, Jun Xie, Naishuo Zhu
Scientific Reports.2017;[Epub] CrossRef
Anti-Cancer Effect of Quercetin in Xenograft Models with EBV-Associated Human Gastric Carcinoma
Hwan Lee, Seulki Lee, Yu Shin, Miyeon Cho, Hyojeung Kang, Hyosun Cho
Molecules.2016; 21(10): 1286. CrossRef
Anti-tumor effect of Inonotus obliquus in xenograft animals with EBV+human gastric carcinoma
Seulki Lee, Hyosun Cho
The Korean Journal of Microbiology.2016; 52(4): 482. CrossRef

Review

REVIEW] Dinoflagellates, Diatoms, and Their Viruses: Keizo Nagasaki; J. Microbiol. 2008;46(3):235-243. Published online July 5, 2008; DOI: https://doi.org/10.1007/s12275-008-0098-y

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Abstract: Since the first discovery of the very high virus abundance in marine environments, a number of researchers were fascinated with the world of “marine viruses”, which had previously been mostly overlooked in studies on marine ecosystems. In the present paper, the possible role of viruses infecting marine eukaryotic microalgae is enlightened, especially summarizing the most up-to-the-minute information of marine viruses infecting bloom-forming dinoflagellates and diatoms. To author’s knowledge, ~40 viruses infecting marine eukaryotic algae have been isolated and characterized to different extents. Among them, a double-stranded DNA (dsDNA) virus “HcV” and a single-stranded RNA (ssRNA) virus “HcRNAV” are the only dinoflagellate-infecting (lytic) viruses that were made into culture; their hosts are a bivalve-killing dinoflagellate Heterocapsa circularisquama. In this article, ecological relationship between H. circularisquama and its viruses is focused. On the other hand, several diatom-infecting viruses were recently isolated and partially characterized; among them, one is infectious to a pen-shaped bloom-forming diatom species Rhizosolenia setigera; some viruses are infectious to genus Chaetoceros which is one of the most abundant and diverse diatom group. Although the ecological relationships between diatoms and their viruses have not been sufficiently elucidated, viral infection is considered to be one of the significant factors affecting dynamics of diatoms in nature. Besides, both the dinoflagellate-infecting viruses and diatom-infecting viruses are so unique from the viewpoint of virus taxonomy; they are remarkably different from any other viruses ever reported. Studies on these viruses lead to an idea that ocean may be a treasury of novel viruses equipped with fascinating functions and ecological roles.

Journal Articles

Hepatitis C Virus Non-structural Protein NS4B Can Modulate an Unfolded Protein Response: Yi Zheng , Bo Gao , Li Ye , Lingbao Kong , Wei Jing , Xiaojun Yang , Zhenghui Wu , Linbai Ye; J. Microbiol. 2005;43(6):529-536.; DOI: https://doi.org/2294 [pii]

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Abstract: Viral infection causes stress to the endoplasmic reticulum (ER). The response to endoplasmic reticulum stress, known as the unfolded protein response (UPR), is designed to eliminate misfolded proteins and allow the cell to recover. The role of hepatitis C virus (HCV) non-structural protein NS4B, a component of the HCV replicons that induce UPR, is incompletely understood. We demonstrate that HCV NS4B could induce activating transcription factor (ATF6) and inositol-requiring enzyme 1 (IRE1), to favor the HCV subreplicon and HCV viral replication. HCV NS4B activated the IRE1 pathway, as indicated by splicing of X box-binding protein (Xbp-1) mRNA. However, transcriptional activation of the XBP-1 target gene, EDEM (ER degradation-enhancing a-mannosidase-like protein, a protein degradation factor), was inhibited. These results imply that NS4B might induce UPR through ATF6 and IRE1-XBP1 pathways, but might also modify the outcome to benefit HCV or HCV subreplicon replication.

Comparative Analysis of Intracellular Trans-Splicing Ribozyme Activity Against Hepatitis C Virus Internal Ribosome Entry Site: Kyung-Ju Ryu Seong-Wook Lee; J. Microbiol. 2004;42(4):361-364.; DOI: https://doi.org/2097 [pii]

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Abstract: Internal ribosome entry site (IRES) of the hepatitis C virus (HCV) is known to be essential for HCV replication and most conserved among HCV variants. Hence, IRES RNA is a good therapeutic target for RNA-based inhibitors, such as ribozymes. We previously proposed a new anti-HCV modulation strategy based on trans-splicing ribozymes, which can selectively replace HCV transcripts with a new RNA that exerts anti-HCV activity. To explore this procedure, sites which are accessible to ribozymes in HCV IRES were previously determined by employing an RNA mapping method in vitro. In this study, we evaluate the intracellular accessibility of the ribozymes by comparing the trans-splicing activities in cells of several ribozymes targeting different sites of the HCV IRES RNA. We assessed the intracellular activities of the ribozymes by monitoring their target-specific induction degree of both reporter gene activity and cytotoxin expression. The ribozyme capable of targeting the most accessible site identified by the mapping studies then harbored the most active trans-splicing activity in cells. These results suggest that the target sites predicted to be accessible are truly the most accessible in the cells, and thus, could be applied to the development of various RNA-based anti-HCV therapies.

Sequence Analysis of NS4 Region of HCV Isolated from Korean Patient: Paik, Sang Hoon , Lee, Young Ik , Kim, Won Bae , Yang, Jai Myung; J. Microbiol. 1995;33(3):260-266.

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Abstract: Hepatitis C virus (HCV) has been considered as a major causative agent of post-transfusion related non-A, non-B hepatitis. In this study, the cDNA sequence of NS4 region of HCV (HCV-S) obtained from a Korean patient's plasma was determined. Comparative nucleotide sequence analysis between to type II. 67.2% homology to type III, and 66.4% homology to type IV. The putative amino acid sequence homologies to types I, II, III, and IV were 82.8-84.7%, 92.5-95.1%. 72.5% and 71.1% respectively. This data strongly suggests that HCV-S should be classified as type II. Significant similarities of hydrophobicity profiles and putative transmembranous domains were found in HCV-S and four major prototypes, indicating that the protein structure is similar in spite of the heterogeneities of intertype homologies at the level of the primary nucleotide and amino acid sequences.

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