Journal Article
- Development and validation of multiplex real-time PCR assays for rapid detection of cytomegalovirus, Epstein-Barr virus, and polyomavirus BK in whole blood from transplant candidates
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Kyung-Ah Hwang , Ji Hoon Ahn , Jae-Hwan Nam
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J. Microbiol. 2018;56(8):593-599. Published online July 25, 2018
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DOI: https://doi.org/10.1007/s12275-018-8273-2
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Abstract
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Transplant recipients are more susceptible to bacterial and
viral infections. Cytomegalovirus (CMV), Epstein-Barr virus
(EBV), and polyomavirus BK (BK) are risk factors for graft
dysfunction. All three of them are latent viruses that can cause
serious disease in immunocompromised patients. Mainly qualitative
PCR tests are required for diagnosis and quantitative
monitoring, which are used to follow the response to transplantation.
We developed a multiplex real-time PCR (qPCR)
method
to detect these viruses during blood screenings of
transplant recipients. We also validated analytical and clinical
performance tests using the developed multiplex qPCR.
The limit of detection (LOD) was 100, 125, and 183 copies/ml
for CMV, EBV, and BK, respectively. These results had high
linearity (R2 = 0.997) and reproducibility (CV range, 0.95–
2.38%, 0.52–3.32%, and 0.31–2.45%, respectively). Among
183 samples, we detected 8 samples that were positive for
CMV, while only 6 were positive for EBV, and 3 were positive
for BK. Therefore, the viral infection prevalence in transplant
candidates was 4.40% for CMV, 3.29% for EBV, and
1.64% for BK. This multiplex qPCR method should be used
widely for diagnosing and monitoring latent viral infections
in transplant recipients.
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Citations
Citations to this article as recorded by

- CRISPR-Cas-mediated diagnostics
Luoxi Li, Guanwang Shen, Min Wu, Jianxin Jiang, Qingyou Xia, Ping Lin
Trends in Biotechnology.2022; 40(11): 1326. CrossRef - An Overview of Laboratory Diagnosis of Central Nervous System Viral Infections
Sharifah Aliah Diyanah Syed Hussin, Ang-Lim Chua, Hassanain Al-Talib, Shamala Devi Sekaran, Seok Mui Wang
Journal of Pure and Applied Microbiology.2022; 16(4): 2225. CrossRef - İnsan sitomegalovirüs/ epstein-barr virüs koenfeksiyonunun kronik hepatit b hastalarının karaciğer fonksiyonları üzerine olası etkileri
Zehra ÖKSÜZ, Mehmet Sami SERİN, Serkan YARAŞ, Enver ÜÇBİLEK, Orhan SEZGİN
Mersin Üniversitesi Sağlık Bilimleri Dergisi.2021; 14(2): 262. CrossRef - Design of InnoPrimers-Duplex Real-Time PCR for Detection and Treatment Response Prediction of EBV-Associated Nasopharyngeal Carcinoma Circulating Genetic Biomarker
Mai Abdel Haleem Abusalah, Siti Asma Binti Hassan, Norhafiza Mat Lazim, Baharudin Abdullah, Wan Fatihah Binti Wan Sohaimi, Azlan Husin, Kueh Yee Cheng, Chan Yean Yean
Diagnostics.2021; 11(10): 1761. CrossRef - Virus Detection: A Review of the Current and Emerging Molecular and Immunological Methods
A. Cassedy, A. Parle-McDermott, R. O’Kennedy
Frontiers in Molecular Biosciences.2021;[Epub] CrossRef - Interferon signature in immunosuppressed patients with lower respiratory tract infections: dosage on bronchoalveolar lavage
Massimiliano Bergallo, Linda Ferrari, Giulia Faolotto, Piero E. Balbo, Paola Montanari, Filippo Patrucco, Francesco Gavelli, Matteo Daverio, Mattia Bellan, Livia Salmi, Luigi M. Castello, Paolo Ravanini
Minerva Medica.2020;[Epub] CrossRef
Review
- [MINIREVIEW] Phylogenetic comparison of Epstein-Barr virus genomes
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Su Jin Choi , Seok Won Jung , Sora Huh , Hyosun Cho , Hyojeung Kang
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J. Microbiol. 2018;56(8):525-533. Published online June 14, 2018
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DOI: https://doi.org/10.1007/s12275-018-8039-x
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59
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Abstract
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Technologies used for genome analysis and whole genome
sequencing are useful for us to understand genomic characterization
and divergence. The Epstein-Barr virus (EBV)
is an oncogenic virus that causes diverse diseases such as
Burkitt’s lymphoma (BL), nasopharyngeal carcinoma (NPC),
Hodgkin’s lymphoma (HL), and gastric carcinoma (GC). EBV
genomes found in these diseases can be classified either by
phases of EBV latency (type-I, -II, and -III latency) or types
of EBNA2 sequence difference (type-I EBV, type-II EBV or
EBV-1, EBV-2). EBV from EBV-transformed lymphoblastoid
cell line (LCL) establishes type-III latency, EBV from NPC
establishes type-II latency, and EBV from GC establishes
type-I latency. However, other important factors play key
roles in classifying numerous EBV strains because EBV genomes
are highly diverse and not phylogenetically related
to types of EBV-associated diseases. Herein, we first reviewed
previous studies to describe molecular characteristics of EBV
genomes. Then, using comparative and phylogenetic analyses,
we phylogenetically analyzed molecular variations of EBV
genomes and proteins. The review of previous studies and
our phylogenetic analysis showed that EBV genomes and
proteins were highly diverse regardless of types of EBV-associated
diseases. Other factors should be considered in determining
EBV taxonomy. This review will be helpful to understand
complicated phylogenetic relationships of EBV genomes.
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Citations
Citations to this article as recorded by

- Mechanistic Understanding of EBV+Lymphoproliferative Disease Development After Transplantation
Philippe L. Furlano, Georg A. Böhmig, Elisabeth Puchhammer-Stöckl, Hannes Vietzen
Transplantation.2024; 108(9): 1867. CrossRef - Aquaporin-3 is down-regulated by LMP1 in nasopharyngeal carcinoma cells to regulate cell migration and affect EBV latent infection
Jing Li, Duo Shi, Zhiyuan Gong, Wen Liu, Yan Zhang, Bing Luo
Virus Genes.2024; 60(5): 488. CrossRef - Characterization of a new CCCTC-binding factor binding site as a dual regulator of Epstein-Barr virus latent infection
Sun Hee Lee, Kyoung-Dong Kim, Miyeon Cho, Sora Huh, Seong Ho An, Donghyun Seo, Kyuhyun Kang, Minhee Lee, Hideki Tanizawa, Inuk Jung, Hyosun Cho, Hyojeung Kang, JJ Miranda
PLOS Pathogens.2023; 19(1): e1011078. CrossRef - Profiling genome-wide recombination in Epstein Barr virus reveals type-specific patterns and associations with endemic-Burkitt lymphoma
Eddy O. Agwati, Cliff I. Oduor, Cyrus Ayieko, John Michael Ong’echa, Ann M. Moormann, Jeffrey A. Bailey
Virology Journal.2022;[Epub] CrossRef - Epstein–Barr Virus (EBV) Epithelial Associated Malignancies: Exploring Pathologies and Current Treatments
Oren Shechter, Daniel G. Sausen, Elisa S. Gallo, Harel Dahari, Ronen Borenstein
International Journal of Molecular Sciences.2022; 23(22): 14389. CrossRef - Current approach and novel perspectives in nasopharyngeal carcinoma: the role of targeting proteasome dysregulation as a molecular landmark in nasopharyngeal cancer
Ramon Yarza, Mateo Bover, Maria Teresa Agulló-Ortuño, Lara Carmen Iglesias-Docampo
Journal of Experimental & Clinical Cancer Research.2021;[Epub] CrossRef - Interplay between Epstein-Barr virus infection and environmental xenobiotic exposure in cancer
Francisco Aguayo, Enrique Boccardo, Alejandro Corvalán, Gloria M. Calaf, Rancés Blanco
Infectious Agents and Cancer.2021;[Epub] CrossRef - Stress-Induced Epstein-Barr Virus Reactivation
Daniel Sausen, Maimoona Bhutta, Elisa Gallo, Harel Dahari, Ronen Borenstein
Biomolecules.2021; 11(9): 1380. CrossRef - Epstein‐Barr virus strain variation and cancer
Teru Kanda, Misako Yajima, Kazufumi Ikuta
Cancer Science.2019; 110(4): 1132. CrossRef - A reliable Epstein-Barr Virus classification based on phylogenomic and population analyses
Louise Zanella, Ismael Riquelme, Kurt Buchegger, Michel Abanto, Carmen Ili, Priscilla Brebi
Scientific Reports.2019;[Epub] CrossRef - Novel Synthetic DNA Immunogens Targeting Latent Expressed Antigens of Epstein–Barr Virus Elicit Potent Cellular Responses and Inhibit Tumor Growth
Krzysztof Wojtak, Alfredo Perales-Puchalt, David B. Weiner
Vaccines.2019; 7(2): 44. CrossRef
Research Support, Non-U.S. Gov'ts
- Characterization of the rapamycin-inducible EBV LMP1 activation system
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Sang Yong Kim , Jung-Eun Kim , Jiyeon Won , Yoon-Jae Song
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J. Microbiol. 2015;53(10):732-738. Published online October 2, 2015
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DOI: https://doi.org/10.1007/s12275-015-5455-z
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55
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6
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Abstract
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Epstein-Barr virus (EBV) latent infection membrane protein
1 (LMP1) is required for EBV-mediated B lymphocyte
transformation into proliferating lymphoblastoid cell lines
(LCL). LMP1 oligomerizes spontaneously in membrane
lipid rafts via its transmembrane domain and constitutively
activates signal transduction pathways, including NF-κB,
p38 Mitogen-Activated Protein Kinase (MAPK), and c-Jun
N-terminal Kinase (JNK). Since LMP1 mimics the tumor necrosis
factor receptor (TNFR), CD40, it may be effectively
utilized to study the effects of constitutive activation of signal
transduction pathways on cellular physiology. On the other
hand, LMP1 presents a disadvantage in terms of determining
the sequential events and factors involved in signaling pathways.
A CD40-LMP1 chimeric molecule has been generated
to overcome this limitation but does not represent the authentic
and physiological nature of LMP1. In the current
study, a ligand-dependent activation system for LMP1 using
rapamycin-inducible dimerization was generated to delineate
the LMP1 signaling pathway.
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Citations
Citations to this article as recorded by

- Antiviral Activities of Ethyl Pheophorbides a and b Isolated from Aster pseudoglehnii against Influenza Viruses
Subin Park, Ji-Young Kim, Hak Cheol Kwon, Dae Sik Jang, Yoon-Jae Song
Molecules.2022; 28(1): 41. CrossRef - Antiviral Activities of Quercetin and Isoquercitrin Against Human Herpesviruses
Chae Hyun Kim, Jung-Eun Kim, Yoon-Jae Song
Molecules.2020; 25(10): 2379. CrossRef - Human Cytomegalovirus IE2 86 kDa Protein Induces STING Degradation and Inhibits cGAMP-Mediated IFN-β Induction
Jung-Eun Kim, Young-Eui Kim, Mark F. Stinski, Jin-Hyun Ahn, Yoon-Jae Song
Frontiers in Microbiology.2017;[Epub] CrossRef - Primary lymphocyte infection models for KSHV and its putative tumorigenesis mechanisms in B cell lymphomas
Sangmin Kang, Jinjong Myoung
Journal of Microbiology.2017; 55(5): 319. CrossRef - Inhibition of human cytomegalovirus immediate-early gene expression and replication by the ethyl acetate (EtOAc) fraction of Elaeocarpus sylvestris in vitro
Sohee Bae, Se Chan Kang, Yoon-Jae Song
BMC Complementary and Alternative Medicine.2017;[Epub] CrossRef - Inhibition of varicella-zoster virus replication by an ethanol extract of Lysimachia mauritiana
Sohee Bae, Yoon-Jae Song
Molecular Medicine Reports.2017; 15(6): 3847. CrossRef
- Genipin as a novel chemical activator of EBV lytic cycle
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Myoungki Son , Minjung Lee , Eunhyun Ryu , Aree Moon , Choon-Sik Jeong , Yong Woo Jung , Gyu Hwan Park , Gi-Ho Sung , Hyosun Cho , Hyojeung Kang
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J. Microbiol. 2015;53(2):155-165. Published online January 28, 2015
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DOI: https://doi.org/10.1007/s12275-015-4672-9
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52
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29
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Abstract
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Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus
that causes acute infection and establishes life-long latency.
EBV causes several human cancers, including Burkitt's lymphoma,
nasopharyngeal and gastric carcinoma. Antiviral
agents can be categorized as virucides, antiviral chemotherapeutic
agents, and immunomodulators. Most antiviral agents
affect actively replicating viruses, but not their latent forms.
Novel antiviral agents must be active on both the replicating
and the latent forms of the virus. Gardenia jasminoides is an
evergreen flowering plant belonging to the Rubiaceae family
and is most commonly found growing wild in Vietnam,
Southern China, Taiwan, Japan, Myanmar, and India. Genipin
is an aglycone derived from an iridoid glycoside called geniposide,
which is present in large quantities in the fruit of
G. jasminoides. In this study, genipin was evaluated for its
role as an antitumor and antiviral agent that produces inhibitory
effects against EBV and EBV associated gastric carcinoma
(EBVaGC). In SNU719 cells, one of EBVaGCs, genipin
caused significant cytotoxicity (70 μM), induced methylation
on EBV C promoter and tumor suppressor gene
BCL7A, arrested cell-cycle progress (S phases), upregulated
EBV latent/lytic genes in a dose-dependent manner, stimulated
EBV progeny production, activated EBV F promoter
for EBV lytic activation, and suppressed EBV infection. These
results
indicated that genipin could be a promising candidate
for antiviral and antitumor agents against EBV and
EBVaGC.
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Citations
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- Research Progress of EB Virus-Associated Gastric Cancer
婷婷 宋
Advances in Clinical Medicine.2024; 14(08): 862. CrossRef - Genipin’s potential as an anti-cancer agent: from phytochemical origins to clinical prospects
Lapava Natallia, Aida Dama, Era Gorica, Karaliova Darya, Sheila I. Peña-Corona, Hernán Cortés, Antonello Santini, Dietrich Büsselberg, Gerardo Leyva-Gómez, Javad Sharifi-Rad
Medical Oncology.2024;[Epub] CrossRef - Update of Natural Products and Their Derivatives Targeting Epstein–Barr Infection
Rosamaria Pennisi, Paola Trischitta, Marianna Costa, Assunta Venuti, Maria Pia Tamburello, Maria Teresa Sciortino
Viruses.2024; 16(1): 124. CrossRef - Genipin-Crosslinking Effects on Biomatrix Development for Cutaneous Wound Healing: A Concise Review
Dewi Utami Nike, Nur Izzah Md Fadilah, Nusaibah Sallehuddin, Ahmad Yasser Hamdi Nor Azlan, Farrah Hani Imran, Manira Maarof, Mh Busra Fauzi
Frontiers in Bioengineering and Biotechnology.2022;[Epub] CrossRef - Genipin, an Inhibitor of UCP2 as a Promising New Anticancer Agent: A Review of the Literature
Young Seok Cho
International Journal of Molecular Sciences.2022; 23(10): 5637. CrossRef - Preparation, characterization, and in vitro release kinetics of doxorubicin-loaded magnetosomes
Shuang Zhang, Xinxin Fan, Guojing Zhang, Weidong Wang, Lei Yan
Journal of Biomaterials Applications.2022; 36(8): 1469. CrossRef - An Integrated Analysis Reveals Geniposide Extracted From Gardenia jasminoides J.Ellis Regulates Calcium Signaling Pathway Essential for Influenza A Virus Replication
Lirun Zhou, Lei Bao, Yaxin Wang, Mengping Chen, Yingying Zhang, Zihan Geng, Ronghua Zhao, Jing Sun, Yanyan Bao, Yujing Shi, Rongmei Yao, Shanshan Guo, Xiaolan Cui
Frontiers in Pharmacology.2021;[Epub] CrossRef - Synthesis of [3H] and [14C]genipin
Adele.E. Queen, David Hesk, David.M. Lindsay, William.J. Kerr, Kenneth Rehder, Tim Fennell, Wayne Mascarella, Desong Zhong, Scott Runyon
Journal of Labelled Compounds and Radiopharmaceuticals.2020; 63(4): 196. CrossRef - Genipin inhibits rotavirus-induced diarrhea by suppressing viral replication and regulating inflammatory responses
Jong-Hwa Kim, Kiyoung Kim, Wonyong Kim
Scientific Reports.2020;[Epub] CrossRef - Genipap (Genipa americana L.) juice intake biomarkers after medium-term consumption
Livia Dickson, Mathieu Tenon, Ljubica Svilar, Pascale Fança-Berthon, Jean-Charles Martin, Hervé Rogez, Fabrice Vaillant
Food Research International.2020; 137: 109375. CrossRef - Evaluation on the antiviral activity of genipin against white spot syndrome virus in crayfish
Ai-Guo Huang, Xiao-Ping Tan, Shen-Ye Qu, Gao-Xue Wang, Bin Zhu
Fish & Shellfish Immunology.2019; 93: 380. CrossRef - Comparative investigation on metabolite changes in ‘wu mi’ production by Vaccinium bracteatum Thunb. leaves based on multivariate data analysis using UPLC–QToF–MS
Mingcong Fan, Yihui Fan, Zhiming Rao, Yan Li, Haifeng Qian, Hui Zhang, Gangcheng Wu, Xiguang Qi, Li Wang
Food Chemistry.2019; 286: 146. CrossRef - Selective oncolytic effect in Epstein-Barr virus (EBV)-associated gastric carcinoma through efficient lytic induction by Euphorbia extracts
Dong-eun Kim, Sunhee Jung, Hyung Won Ryu, Miri Choi, Mingu Kang, Hyunju Kang, Heung Joo Yuk, Hyejeong Jeong, Jiyeon Baek, Jae-Hyoung Song, Janghwan Kim, Hyojeung Kang, Sang-Bae Han, Sei-Ryang Oh, Sungchan Cho
Journal of Functional Foods.2018; 42: 146. CrossRef - Curcuminoids as EBV Lytic Activators for Adjuvant Treatment in EBV-Positive Carcinomas
Octavia Ramayanti, Mitch Brinkkemper, Sandra Verkuijlen, Leni Ritmaleni, Mei Go, Jaap Middeldorp
Cancers.2018; 10(4): 89. CrossRef - EBV transformation induces overexpression of hMSH2/3/6 on B lymphocytes and enhances γδT‐cell‐mediated cytotoxicity via TCR and NKG2D
Yu‐mei Dai, Hai‐ying Liu, Yun‐feng Liu, Yuan Zhang, Wei He
Immunology.2018; 154(4): 673. CrossRef - Infection‐associated epigenetic alterations in gastric cancer: New insight in cancer therapy
Sadegh Fattahi, Mohadeseh Kosari‐Monfared, Elham Ghadami, Monireh Golpour, Parastoo Khodadadi, Mohammad Ghasemiyan, Haleh Akhavan‐Niaki
Journal of Cellular Physiology.2018; 233(12): 9261. CrossRef - Plant-Derived Anticancer Agents: Lessons from the Pharmacology of Geniposide and Its Aglycone, Genipin
Solomon Habtemariam, Giovanni Lentini
Biomedicines.2018; 6(2): 39. CrossRef - Main Human Urinary Metabolites after Genipap (Genipa americana L.) Juice Intake
Livia Dickson, Mathieu Tenon, Ljubica Svilar, Pascale Fança-Berthon, Raphael Lugan, Jean-Charles Martin, Fabrice Vaillant, Hervé Rogez
Nutrients.2018; 10(9): 1155. CrossRef - Genipin: A natural blue pigment for food and health purposes
Iramaia Angélica Neri-Numa, Marina Gabriel Pessoa, Bruno Nicolau Paulino, Glaucia Maria Pastore
Trends in Food Science & Technology.2017; 67: 271. CrossRef - Geniposide and geniposidic acid, modified forms of genipin, attenuate genipin-induced mitochondrial apoptosis without altering the anti-inflammatory ability in KGN cell line
Tao Zuo, Wenming Xu, Henli Li, Hang Song, Minghui Zhu
Medicinal Chemistry Research.2017; 26(2): 499. CrossRef - Primary lymphocyte infection models for KSHV and its putative tumorigenesis mechanisms in B cell lymphomas
Sangmin Kang, Jinjong Myoung
Journal of Microbiology.2017; 55(5): 319. CrossRef - Expression of toll‐like receptors in T lymphocytes stimulated with N‐(3‐oxododecanoyl)‐L‐homoserine lactone from Pseudomonas aeruginosa
Lei Bao, Jialin Yu, Haiying Zhong, Daochao Huang, Qi Lu
APMIS.2017; 125(6): 553. CrossRef - Chemical Constituents from the Flowers of Wild Gardenia jasminoides J.Ellis
Hu Zhang, Ning Feng, Yan‐Tong Xu, Tian‐Xiang Li, Xiu‐Mei Gao, Yan Zhu, Yun Seon Song, Ya‐Nan Wang, Hong‐Hua Wu
Chemistry & Biodiversity.2017;[Epub] CrossRef - The Suppressive Effects of Geniposide and Genipin on Helicobacter pylori Infections In Vitro and In Vivo
Chiung‐Hung Chang, Jin‐Bin Wu, Jai‐Sing Yang, Yen‐Ju Lai, Chiu‐Hsian Su, Chi‐Cheng Lu, Yuan‐Man Hsu
Journal of Food Science.2017; 82(12): 3021. CrossRef - Antitumor Effects of Genipin: New and Emerging Insights from Recent Studies
Yu Su Shin, Miyeon Cho, Gyu Hwan Park, Hyosun Cho, Hyojeung Kang
Journal of Bacteriology and Virology.2016; 46(2): 108. CrossRef - Iridoids are natural glycation inhibitors
Brett J. West, Shixin Deng, Akemi Uwaya, Fumiyuki Isami, Yumi Abe, Sho-ichi Yamagishi, C. Jarakae Jensen
Glycoconjugate Journal.2016; 33(4): 671. CrossRef - Genipin Enhances Kaposi’s Sarcoma-Associated Herpesvirus Genome Maintenance
Miyeon Cho, Seok Won Jung, Soomin Lee, Kuwon Son, Gyu Hwan Park, Jong-Wha Jung, Yu Su Shin, Taegun Seo, Hyosun Cho, Hyojeung Kang, Shou-Jiang Gao
PLOS ONE.2016; 11(10): e0163693. CrossRef - Anti-cancer effect of Cordyceps militaris in human colorectal carcinoma RKO cells via cell cycle arrest and mitochondrial apoptosis
Hwan Hee Lee, Seulki Lee, Kanghyo Lee, Yu Su Shin, Hyojeung Kang, Hyosun Cho
DARU Journal of Pharmaceutical Sciences.2015;[Epub] CrossRef - 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
Journal of Microbiology.2015; 53(7): 468. CrossRef
- Hypermethylation of the interferon regulatory factor 5 promoter in Epstein-Barr virus-associated gastric carcinoma
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Seung Myung Dong , Hyun Gyu Lee , Sung-Gyu Cho , Seung-Hyun Kwon , Heejei Yoon , Hyun-Jin Kwon , Ji Hae Lee , Hyemi Kim , Pil-Gu Park , Hoguen Kim , S. Diane Hayward , Jeon Han Park , Jae Myun Lee
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J. Microbiol. 2015;53(1):70-76. Published online January 4, 2015
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DOI: https://doi.org/10.1007/s12275-014-4654-3
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49
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Abstract
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Interferon regulatory factor-5 (IRF-5), a member of the mammalian
IRF transcription factor family, is regulated by p53,
type I interferon and virus infection. IRF-5 participates in
virus-induced TLR-mediated innate immune responses and
may play a role as a tumor suppressor. It was suppressed in
various EBV-infected transformed cells, thus it is valuable to
identify the suppression mechanism. We focused on a promoter
CpG islands methylation, a kind of epigenetic regulation
in EBV-associated Burkitt’s lymphomas (BLs) and gastric
carcinomas. IRF-5 is not detected in most of EBV-infected
BL cell lines due to hypermethylation of IRF-5 distal
promoter (promoter-A), which was restored by a demethylating
agent, 5-aza-2-deoxycytidine. Hypomethylation of
CpG islands in promoter-A was observed only in EBV type III
latent infected BL cell lines (LCL and Mutu III). Similarly,
during EBV infection to Akata-4E3 cells, IRF-5 was observed
at early time periods (2 days to 8 weeks), concomitant unmethylation
of promoter-A, but suppressed in later infection
periods as observed in latency I BL cell lines. Moreover, hypermethylation
in IRF-5 promoter-A region was also observed
in EBV-associated gastric carcinoma (EBVaGC) cell lines or
primary gastric carcinoma tissues, which show type I latent
infection. In summary, IRF-5 is suppressed by hypermethylation
of its promoter-A in most of EBV-infected transformed
cells, especially BLs and EBVaGC. EBV-induced carcinogenesis
takes an advantage of proliferative effects of TLR
signaling, while limiting IRF-5 mediated negative effects in
the establishment of EBVaGCs.
-
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- Epstein–Barr Virus and gastric carcinoma pathogenesis with emphasis on underlying epigenetic mechanisms
Fatemeh Estaji, Saeed Zibaee, Maryam Torabi, Sharareh Moghim
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Mincong Liang, Weiqiang Pan, Yanlin You, Xiaowei Qin, Hualong Su, Zhipeng Zhan, Shaoping Weng, Changjun Guo, Jianguo He
Communications Biology.2024;[Epub] CrossRef - Role of interferon regulatory factor 5 (IRF5) in tumor progression: Prognostic and therapeutic potential
Bailey K. Roberts, Gilbert Collado, Betsy J. Barnes
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2024; 1879(1): 189061. CrossRef - IRF5 suppresses metastasis through the regulation of tumor-derived extracellular vesicles and pre-metastatic niche formation
Bailey K. Roberts, Dan Iris Li, Carter Somerville, Bharati Matta, Vaishali Jha, Adison Steinke, Zarina Brune, Lionel Blanc, Samuel Z. Soffer, Betsy J. Barnes
Scientific Reports.2024;[Epub] CrossRef - Virus-induced host genomic remodeling dysregulates gene expression, triggering tumorigenesis
Weixia Dong, Huiqin Wang, Menghui Li, Ping Li, Shaoping Ji
Frontiers in Cellular and Infection Microbiology.2024;[Epub] CrossRef - Virus hijacking of host epigenetic machinery to impair immune response
Maëlle Locatelli, Suzanne Faure-Dupuy, Britt A. Glaunsinger
Journal of Virology.2023;[Epub] CrossRef - Genetic dysregulation of immunologic and oncogenic signaling pathways associated with tumor-intrinsic immune resistance: a molecular basis for combination targeted therapy-immunotherapy for cancer
Kristian M. Hargadon
Cellular and Molecular Life Sciences.2023;[Epub] CrossRef - Epigenetics of Epstein Barr virus — A review
Gadde Shareena, Dileep Kumar
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2023; 1869(8): 166838. CrossRef - Transcriptome Sequencing Highlights the Regulatory Role of DNA Methylation in Immune-Related Genes’ Expression of Chinese Oak Silkworm, Antheraea pernyi
Saima Kausar, Ruochen Liu, Isma Gul, Muhammad Nadeem Abbas, Hongjuan Cui
Insects.2022; 13(3): 296. CrossRef - Interferon regulatory factor 5‑induced upregulation of zinc‑finger protein 217 promotes pancreatic carcinoma progression
Xiao Qiao, Shengxiang Lv, Yan Qiao, Fei Wang, Lin Miao
Molecular Medicine Reports.2022;[Epub] CrossRef - A Novel Cognition of Decitabine: Insights into Immunomodulation and Antiviral Effects
Ji Xiao, Ping Liu, Yiliang Wang, Yexuan Zhu, Qiongzhen Zeng, Xiao Hu, Zhe Ren, Yifei Wang
Molecules.2022; 27(6): 1973. CrossRef - Epstein–Barr Virus Epithelial Cancers—A Comprehensive Understanding to Drive Novel Therapies
Shuting Han, Joshua K. Tay, Celestine Jia Ling Loh, Axel Jun Ming Chu, Joe Poh Sheng Yeong, Chwee Ming Lim, Han Chong Toh
Frontiers in Immunology.2021;[Epub] CrossRef - The Impact of Epstein-Barr Virus Infection on Epigenetic Regulation of Host Cell Gene Expression in Epithelial and Lymphocytic Malignancies
Merrin Man Long Leong, Maria Li Lung
Frontiers in Oncology.2021;[Epub] CrossRef - Targeting the signaling in Epstein–Barr virus-associated diseases: mechanism, regulation, and clinical study
Ya Cao, Longlong Xie, Feng Shi, Min Tang, Yueshuo Li, Jianmin Hu, Lin Zhao, Luqing Zhao, Xinfang Yu, Xiangjian Luo, Weihua Liao, Ann M. Bode
Signal Transduction and Targeted Therapy.2021;[Epub] CrossRef - Aberrantly Methylated-Differentially Expressed Genes and Pathways in Epstein–Barr Virus-Associated Gastric Cancer
Jing-jing Jing, Hao Li, Ze-yang Wang, Heng Zhou, Li-ping Sun, Yuan Yuan
Future Oncology.2020; 16(6): 187. CrossRef - P53 in the impaired lungs
Mohammad A. Uddin, Nektarios Barabutis
DNA Repair.2020; 95: 102952. CrossRef - DNA methylomes and transcriptomes analysis reveal implication of host DNA methylation machinery in BmNPV proliferation in Bombyx mori
Haoling Huang, Ping Wu, Shaolun Zhang, Qi Shang, Haotong Yin, Qirui Hou, Jinbo Zhong, Xijie Guo
BMC Genomics.2019;[Epub] CrossRef - Evidence from genome wide association studies implicates reduced control of Epstein-Barr virus infection in multiple sclerosis susceptibility
Ali Afrasiabi, Grant P. Parnell, Nicole Fewings, Stephen D. Schibeci, Monica A. Basuki, Ramya Chandramohan, Yuan Zhou, Bruce Taylor, David A. Brown, Sanjay Swaminathan, Fiona C. McKay, Graeme J. Stewart, David R. Booth
Genome Medicine.2019;[Epub] CrossRef - Epigenetic View on Interferon γ Signalling in Tumour Cells
E. Selinger, Milan Reiniš
Folia Biologica.2018; 64(4): 125. CrossRef - DNA Tumor Virus Regulation of Host DNA Methylation and Its Implications for Immune Evasion and Oncogenesis
Sharon Kuss-Duerkop, Joseph Westrich, Dohun Pyeon
Viruses.2018; 10(2): 82. CrossRef - DNA hypermethylation induced by Epstein-Barr virus in the development of Epstein-Barr virus-associated gastric carcinoma
Su Jin Choi, Yu Su Shin, Byung Woog Kang, Jong Gwang Kim, Kyoung-Jae Won, Paul M. Lieberman, Hyosun Cho, Hyojeung Kang
Archives of Pharmacal Research.2017; 40(8): 894. CrossRef - The Role of Epigenetic Regulation in Epstein-Barr Virus-Associated Gastric Cancer
Jun Nishikawa, Hisashi Iizasa, Hironori Yoshiyama, Munetaka Nakamura, Mari Saito, Sho Sasaki, Kanami Shimokuri, Masashi Yanagihara, Kouhei Sakai, Yutaka Suehiro, Takahiro Yamasaki, Isao Sakaida
International Journal of Molecular Sciences.2017; 18(8): 1606. CrossRef - Primary lymphocyte infection models for KSHV and its putative tumorigenesis mechanisms in B cell lymphomas
Sangmin Kang, Jinjong Myoung
Journal of Microbiology.2017; 55(5): 319. CrossRef
- Sequence Analysis of the Latent Membrane Protein 1 Genes of Epstein-Barr Virus isolataes in Korea
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Cho, Shin , Cho, Sung Gyu , Shim, Young Shik , Lee, Won Keun
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J. Microbiol. 1998;36(2):130-138.
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Abstract
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The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is essential for Blymphocyte transformation, and activates NF-kB transcription factior in lymphocytes. LMP1 genes were isolated and sequenced from three type 1 isolates (SNU-321, SNU-538, and SNU-1103) and a type 2 isolate (SNU-20), all derived from Korean cancer pstients, to assess sequence variations in the LMP1 of Korean EBV isolates. Sequence analysis revealed that the SNU-1103 and SNU-20 LNP1 genes were nearly identical to that of the prototype B95-8 type 1 EBV strain, with 98% and 96% identities at the nucleotide and protein level, respectively. The SNU-321 and SNU-538 type 1 LMP1 genes both had a G to T substitution at nucleotide position 169,426, resulting in the loss of a XhoI site, and a carboxy-termina 30 base pair deletion (position 168,287-168,256), indicating they were variant LMP1 genes, as initially described in a Chinese nasopharyngeal carcinoma-derived EBV isolate (CAO). These two variant LMP1 genes shared more sequence variations than the SNU-20 and SNU-1103 IMP1 geres presumably associated with the LMP1 XhoI polymorphism, and showed 96% and 94% sequence identities, respectively, at the nucleotide and amino acid level to respective sequences of B95-8. There were consistent variations between all four isolates and B95-8, including 8-amino acid changes (B95-8 residues 85, 122, 129, 222, 309, 312, 334, 338, and 366) and a 5-amino acid deletion in the carboxy-terminal third 11-amino acid repeat. Transfection of each of these cloned LMP1 genes into Jurkat cells resulted in tenfold stimulation of NF-kB activity, confirming functionality of LMP1 proteins expressed from these genes. Taken together, these results indicate that there is a high degree of overall conservation in sequences of LMP1 between different EBV isolates, yet the distinct sequence variation patterns are consistent with the notion that there are at least two distinct LMP1 variants.
- Deletion Analysis of the Major NF-[kappa]B Activation Domain in Latent Membrane Protein 1 of Epstein-Barr Virus
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Shin Cho , Won-Keun Lee
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J. Microbiol. 1999;37(4):256-262.
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Abstract
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Latent membrane protein 1 (LMP1) of the Epstein-Barr virus (EBV) is an integral membrane protein with six transmembrane domains, which is essential for EBV-induced B cell transformation. LMP1 functions as a constitutively active tumor necrosis factor receptor (TNFR) like membrane receptor, whose signaling requires recruitment of TNFR-associated factors (TRAFs) and leads to NF-[kappa]B activation. NF-[kappa]B activation by LMP1 is critical for B cell transformation and has been linked to many phenotypic changes associated with EBV-induced B cell transformation. Deletion analysis has identified two NF-[kappa]B activation regions in the carboxy terminal cytoplasmic domains of LMP1, termed CTAR1 (residues 194-232) and CTAR2 (351-386). The membrane proximal C-terminal domain was precisely mapped to a PXQXT motif (residues 204-208) involved in TRAF binding as well as NF-[kappa]B activation. In this study, we dissected the CTAR2 region, which is the major NF-[kappa]B signaling effector of LMP1, to determine a minimal functional sequence. A series of LMP1 mutant constructs systematically deleted for the CTAR2 region were prepared, and NF-[kappa]B activation activity of these mutants were assessed by transiently expressing them in 293 cells and Jurkat T cells. The NF-[kappa]B activation domain of CTAR2 appears to reside in a stretch of 6 amino acids (residues 379-384) at the end of the carboxy terminus.
- High Prevalence of the China 1 Strain of Epstein-Barr Virus in Korea as Determined by Sequence Polymorphisms in the Carboxy-Terminal Tail of LMP1
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Sung-Gyu Cho , Won-Keun Lee
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J. Microbiol. 2003;41(2):129-136.
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Abstract
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The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) exhibits considerable sequence heterogeneity among EBV isolates. Seven distinct EBV strains have been defined based on sequence polymorphisms in the LMP1 gene, which are designated China 1, China 2, China 3, Alaskan, Mediterranean, NC, and the B95-8 strains. In this study, we analyzed a 30-bp deletion and sequence variations in the carboxy-terminal region of the LMP1 gene in 12 EBV isolates from spontaneous lymphoblastoid cell lines derived from individuals with non-EBV associated cancers in Korea. Eleven of the 12 isolates showed a 30-bp deletion spanning LMP1 amino acids 342 to 353, suggesting a high prevalence of the LMP1 30-bp deletion variant among EBV isolates in Korea. In addition, all 12 isolates had a 15-bp common deletion in the 33-bp repeat region and multiple base-pair changes relative to the prototype B95-8 EBV strain along with variations in the number of the 33-bp repeats. The bp changes at positions 168746, 168694, 168687, 168395, 168357, 168355, 168631, 168320, 168308, 168295, and 168225 were highly conserved among the isolates. Comparative analysis of sequence change patterns in the LMP1 carboxy-terminal coding region identified nine 30-bp deletion variants as China 1, two deletion variants as a possible interstrain between the Alaskan and China 1 strains, and a single undeleted variant as a possible variant of the Alaskan strain. These results suggest the predominance of the China 1 EBV strain in the Korean population.