Journal of Microbiology

Journal Articles

The Regulation of Phosphorus Release by Penicillium chrysogenum in Different Phosphate via the TCA Cycle and Mycelial Morphology: Liyan Wang , Da Tian , Xiaoru Zhang , Mingxue Han , Xiaohui Cheng , Xinxin Ye , Chaochun Zhang , Hongjian Gao , Zhen Li; J. Microbiol. 2023;61(8):765-775. Published online September 4, 2023; DOI: https://doi.org/10.1007/s12275-023-00072-2

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Abstract: Phosphate-solubilizing fungi (PSF) efficiently dissolve insoluble phosphates through the production of organic acids. This study investigates the mechanisms of organic acid secretion by PSF, specifically Penicillium chrysogenum, under tricalcium phosphate ( Ca3(PO4)2, Ca–P) and ferric phosphate ( FePO4, Fe–P) conditions. Penicillium chrysogenum exhibited higher phosphorus (P) release efficiency from Ca-P (693.6 mg/L) than from Fe–P (162.6 mg/L). However, Fe–P significantly enhanced oxalic acid (1193.7 mg/L) and citric acid (227.7 mg/L) production by Penicillium chrysogenum compared with Ca–P (905.7 and 3.5 mg/L, respectively). The presence of Fe–P upregulated the expression of genes and activity of enzymes related to the tricarboxylic acid cycle, including pyruvate dehydrogenase and citrate synthase. Additionally, Fe–P upregulated the expression of chitinase and endoglucanase genes, inducing a transformation of Penicillium chrysogenum mycelial morphology from pellet to filamentous. The filamentous morphology exhibited higher efficiency in oxalic acid secretion and P release from Fe–P and Ca–P. Compared with pellet morphology, filamentous morphology enhanced P release capacity by > 40% and > 18% in Ca–P and Fe–P, respectively. This study explored the strategies employed by PSF to improve the dissolution of different insoluble phosphates.

The comparison of microbial communities in thyroid tissues from thyroid carcinoma patients: Chen-Jian Liu , Si-Qian Chen , Si-Yao Zhang , Jia-Lun Wang , Xiao-Dan Tang , Kun-Xian Yang , Xiao-Ran Li; J. Microbiol. 2021;59(11):988-1001. Published online October 6, 2021; DOI: https://doi.org/10.1007/s12275-021-1271-9

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Thyroid carcinoma is a common endocrine organ cancer associated with abnormal hormone secretion, leading to the disorder of metabolism. The intestinal microbiota is vital to maintain digestive and immunologic homeostasis. The relevant information of the microbial community in the gut and thyroid, including composition, structure, and relationship, is unclear in thyroid carcinoma patients. A total of 93 samples from 25 patients were included in this study. The results showed that microbial communities existed in thyroid tissue; gut and thyroid had high abundance of facultative anaerobes from the Proteobacteria phyla. The microbial metabolism from the thyroid and gut may be affected by the thyroid carcinoma cells. The cooccurrence network showed that the margins of different thyroid tissues were unique areas with more competition; the stabilization of microcommunities from tissue and stool may be maintained by several clusters of species that may execute different vital metabolism processes dominantly that are attributed to the microenvironment of cancer.

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Modulation of Intestinal Flora: a Novel Immunotherapeutic Approach for Enhancing Thyroid Cancer Treatment
Weiqiang Huang, Tao Jiang, Jiaxuan He, Jing Ruan, Baihui Wu, Runchao Tao, Peiye Xu, Yongpan Wang, Rongbing Chen, Hanbing Wang, Qinsi Yang, Kun Zhang, Libo Jin, Da Sun, Jinfeng You
Probiotics and Antimicrobial Proteins.2025;[Epub] CrossRef
Recent advances in gut microbiota and thyroid disease: pathogenesis and therapeutics in autoimmune, neoplastic, and nodular conditions
Lihua Fang, Jie Ning
Frontiers in Cellular and Infection Microbiology.2024;[Epub] CrossRef
Causal relationship of genetically predicted gut microbiota with thyroid cancer: a bidirectional two-sample mendelian randomization study
Xiaohe Sun, Shuai Chen, Shuoqi Zhao, Jingwen Wang, Haibo Cheng
Frontiers in Endocrinology.2024;[Epub] CrossRef
Investigating the role of the intratumoral microbiome in thyroid cancer development and progression
Hanieh Ataollahi, Mehdi Hedayati, Noosha Zia-Jahromi, Maryam Daneshpour, Seyed Davar Siadat
Critical Reviews in Oncology/Hematology.2024; 204: 104545. CrossRef
The relationship between thyroid and human-associated microbiota: A systematic review of reviews
Camilla Virili, Ilaria Stramazzo, Maria Flavia Bagaglini, Anna Lucia Carretti, Silvia Capriello, Francesco Romanelli, Pierpaolo Trimboli, Marco Centanni
Reviews in Endocrine and Metabolic Disorders.2024; 25(1): 215. CrossRef
Clinical potential of microbiota in thyroid cancer therapy
Zilan Xie, Jiating Zhou, Xuan Zhang, Zhi Li
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2024; 1870(2): 166971. CrossRef
Recent Trends and Potential of Radiotherapy in the Treatment of Anaplastic Thyroid Cancer
Kazumasa Sekihara, Hidetomo Himuro, Soji Toda, Nao Saito, Ryoichi Hirayama, Nobuyasu Suganuma, Tetsuro Sasada, Daisuke Hoshino
Biomedicines.2024; 12(6): 1286. CrossRef
Intratumoral Bacteria Dysbiosis Is Associated with Human Papillary Thyroid Cancer and Correlated with Oncogenic Signaling Pathways
Shuang Yu, Yanqiang Ding, Xuejie Wang, Siu Kin Ng, Siting Cao, Weixin Liu, Zhuming Guo, Yubin Xie, Shubin Hong, Lixia Xu, Xiaoxing Li, Jie Li, Weiming Lv, Sui Peng, Yanbing Li, Joseph J.Y. Sung, Jun Yu, Haipeng Xiao
Engineering.2023; 28: 179. CrossRef
Causal analysis of the gut microbiota in differentiated thyroid carcinoma: a two-sample Mendelian randomization study
Zheng Quan, Xiaoyu Zhang, Shilong Wang, Yong Meng
Frontiers in Genetics.2023;[Epub] CrossRef
Tumor Microbial Communities and Thyroid Cancer Development—The Protective Role of Antioxidant Nutrients: Application Strategies and Future Directions
Francesca Gorini, Alessandro Tonacci
Antioxidants.2023; 12(10): 1898. CrossRef
Interaction of Gut Microbiota with Endocrine Homeostasis and Thyroid Cancer
Qi Liu, Wei Sun, Hao Zhang
Cancers.2022; 14(11): 2656. CrossRef

Proteomic analysis reveals the temperature-dependent presence of extracytoplasmic peptidases in the biofilm exoproteome of Listeria monocytogenes EGD-e: Yue-Jia Lee , Chinling Wang; J. Microbiol. 2020;58(9):761-771. Published online July 27, 2020; DOI: https://doi.org/10.1007/s12275-020-9522-8

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Abstract

The foodborne pathogen Listeria monocytogenes resists environmental stresses by forming biofilms. Because this pathogen transmits between the environment and the host, it must adapt to temperature as an environmental stress. In this study, we aimed to identify which proteins were present depending on the temperature in the biofilms of L. monocytogenes EGD-e. Proteins in the supernatants of biofilms formed at 25°C and 37°C were compared using two-dimensional gel electrophoresis and liquid chromatography with tandem mass spectrometry. The larger number of extracytoplasmic proteins associated with cell wall/membrane/envelop biogenesis was identified from the supernatant of biofilms formed at 25°C (7) than those at 37°C (0). Among the 16 extracytoplasmic proteins detected only at 25°C, three were peptidases, namely Spl, Cwh, and Lmo0186. Moreover, mRNA expression of the three peptidases was higher at 25°C than at 37°C. Interestingly, this adaptation of gene expression to temperature was present in sessile cells but not in dispersed cells. After inhibiting the activity of extracytoplasmic peptidases with a protease inhibitor, we noted that the levels of biofilm biomass increased with higher concentrations of the protease inhibitor only when L. monocytogenes grew biofilms at 25°C and not at 37°C. Overall, our data suggest an effect of temperature on the presence of peptidases in L. monocytogenes biofilms. Additionally, increasing the levels of extracytoplasmic peptidases in biofilms is likely a unique feature for sessile L. monocytogenes that causes a naturally occurring breakdown of biofilms and facilitates the pathogen exiting biofilms and disseminating into the environment.

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Stress Adaptation Responses of a Listeria monocytogenes 1/2a Strain via Proteome Profiling
Federica D’Onofrio, Maria Schirone, Antonello Paparella, Ivanka Krasteva, Manuela Tittarelli, Francesco Pomilio, Luigi Iannetti, Nicola D’Alterio, Mirella Luciani
Foods.2023; 12(11): 2166. CrossRef
How to study biofilms: technological advancements in clinical biofilm research
Leanne Cleaver, James A. Garnett
Frontiers in Cellular and Infection Microbiology.2023;[Epub] CrossRef
Studying the metabolic factors that may impact the growth of co-cultured Listeria monocytogenes strains at low temperature
Maria A. Gkerekou, Eleftheria H. Kaparakou, Petros A. Tarantilis, Panagiotis N. Skandamis
Food Research International.2023; 171: 113056. CrossRef
Exoproteome Perspective on the Bile Stress Response of Lactobacillus johnsonii
Bernadette B. Bagon, Valerie Diane V. Valeriano, Ju Kyoung Oh, Edward Alain B. Pajarillo, Ji Yoon Lee, Dae-Kyung Kang
Proteomes.2021; 9(1): 10. CrossRef

Review

Regulation of the AcrAB efflux system by the quorum-sensing regulator AnoR in Acinetobacter nosocomialis: Bindu Subhadra , Surya Surendran , Bo Ra Lim , Jong Sung Yim , Dong Ho Kim , Kyungho Woo , Hwa-Jung Kim , Man Hwan Oh , Chul Hee Choi; J. Microbiol. 2020;58(6):507-518. Published online May 27, 2020; DOI: https://doi.org/10.1007/s12275-020-0185-2

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Abstract

Multidrug efflux pumps play an important role in antimicrobial resistance and pathogenicity in bacteria. Here, we report the functional characterization of the RND (resistance-nodulation- division) efflux pump, AcrAB, in Acinetobacter nosocomialis. An in silico analysis revealed that homologues of the AcrAB efflux pump, comprising AcrA and AcrB, are widely distributed among different bacterial species. Deletion of acrA and/or acrB genes led to decreased biofilm/pellicle formation and reduced antimicrobial resistance in A. nosocomialis. RNA sequencing and mRNA expression analyses showed that expression of acrA/B was downregulated in a quorum sensing (QS) regulator (anoR)-deletion mutant, indicating transcriptional activation of the acrAB operon by AnoR in A. nosocomialis. Bioassays showed that secretion of N-acyl homoserine lactones (AHLs) was unaffected in acrA and acrB deletion mutants; however, AHL secretion was limited in a deletion mutant of acrR, encoding the acrAB regulator, AcrR. An in silico analysis indicated the presence of AcrR-binding motifs in promoter regions of anoI (encoding AHL synthase) and anoR. Specific binding of AcrR was confirmed by electrophoretic mobility shift assays, which revealed that AcrR binds to positions -214 and -217 bp upstream of the translational start sites of anoI and anoR, respectively, demonstrating transcriptional regulation of these QS genes by AcrR. The current study further addresses the possibility that AcrAB is controlled by the osmotic stress regulator, OmpR, in A. nosocomialis. Our data demonstrate that the AcrAB efflux pump plays a crucial role in biofilm/pellicle formation and antimicrobial resistance in A. nosocomialis, and is under the transcriptional control of a number of regulators. In addition, the study emphasizes the interrelationship of QS and AcrAB efflux systems in A. nosocomialis.

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Types and Mechanisms of Efflux Pump Systems and the Potential of Efflux Pump Inhibitors in the Restoration of Antimicrobial Susceptibility, with a Special Reference to Acinetobacter baumannii
Kira M. Zack, Trent Sorenson, Suresh G. Joshi
Pathogens.2024; 13(3): 197. CrossRef
Lysine Trimethylation in Planktonic and Pellicle Modes of Growth in Acinetobacter baumannii
Nicolas Nalpas, Takfarinas Kentache, Emmanuelle Dé, Julie Hardouin
Journal of Proteome Research.2023; 22(7): 2339. CrossRef
The Mechanism of Tigecycline Resistance in Acinetobacter baumannii Revealed by Proteomic and Genomic Analysis
Cunwei Liu, Lei Wang, Ping Wang, Di Xiao, Qinghua Zou
International Journal of Molecular Sciences.2023; 24(10): 8652. CrossRef
Antimicrobial photodynamic therapy against oral biofilm: influencing factors, mechanisms, and combined actions with other strategies
Yijun Li, Guanwen Sun, Jingchan Xie, Suli Xiao, Chen Lin
Frontiers in Microbiology.2023;[Epub] CrossRef
The multifaceted genusAcinetobacter: from infection to bioremediation
Ujwal Dahal, Karan Paul, Shelly Gupta
Journal of Applied Microbiology.2023;[Epub] CrossRef
Efflux pumps and microbial biofilm formation
Mahdyeh Neghabi Hajiagha, Hossein Samadi Kafil
Infection, Genetics and Evolution.2023; 112: 105459. CrossRef
Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria
Ronit Vogt Sionov, Doron Steinberg
Microorganisms.2022; 10(6): 1239. CrossRef
Evidence for Complex Interplay between Quorum Sensing and Antibiotic Resistance in Pseudomonas aeruginosa
Rakesh Sikdar, Mikael H. Elias, Giordano Rampioni
Microbiology Spectrum.2022;[Epub] CrossRef
Update on Multidrug Resistance Efflux Pumps in Acinetobacter spp.
Vanessa Kornelsen, Ayush Kumar
Antimicrobial Agents and Chemotherapy.2021;[Epub] CrossRef
Orthopedic Implant-Related Biofilm Pathophysiology: A Review of the Literature
Meletis Rozis, Dimitrios S Evangelopoulos, Spyros G Pneumaticos
Cureus.2021;[Epub] CrossRef
The impact of cell structure, metabolism and group behavior for the survival of bacteria under stress conditions
Xinyi Zhang, Zhendong Li, Shengmei Pang, Boyu Jiang, Yang Yang, Qiangde Duan, Guoqiang Zhu
Archives of Microbiology.2021; 203(2): 431. CrossRef

Journal Articles

Methyltransferase of a cell culture-adapted hepatitis E inhibits the MDA5 receptor signaling pathway: Jinjong Myoung , Jeong Yoon Lee , Kang Sang Min; J. Microbiol. 2019;57(12):1126-1131. Published online November 22, 2019; DOI: https://doi.org/10.1007/s12275-019-9478-8

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Abstract

Hepatitis E virus (HEV) is a causative agent of acute hepatitis and jaundice. The number of human infections is approximated to be over 20 million cases per year. The transmission is mainly via the fecal-oral route and contaminated water and food are considered to be a major source of infection. As a mouse model is not available, a recent development of a cell culture-adapted HEV strain (47832c) is considered as a very important tools for molecular analysis of HEV pathogenesis in cells. Previously, we demonstrated that HEV-encoded methyltransferase (MeT) encoded by the 47832c strain inhibits MDA5- and RIG-I-mediated activation of interferon β (IFN-β) promoter. Here, we report that MeT impairs the phosphorylation and activation of interferon regulatory factor 3 and the p65 subunit of NF-κB in a dose-dependent manner. In addition, the MeT encoded by the 47832c, but not that of HEV clinical or field isolates (SAR-55, Mex-14, KC-1, and ZJ-1), displays the inhibitory effect. A deeper understanding of MeTmediated suppression of IFN-β expression would provide basis of the cell culture adaptation of HEV.

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Viral Hepatitis: Host Immune Interaction, Pathogenesis and New Therapeutic Strategies
Angela Quirino, Nadia Marascio, Francesco Branda, Alessandra Ciccozzi, Chiara Romano, Chiara Locci, Ilenia Azzena, Noemi Pascale, Grazia Pavia, Giovanni Matera, Marco Casu, Daria Sanna, Marta Giovanetti, Giancarlo Ceccarelli, Pierfrancesco Alaimo di Loro,
Pathogens.2024; 13(9): 766. CrossRef
Hepatitis E virus: from innate sensing to adaptive immune responses
Yannick Brüggemann, Mara Klöhn, Heiner Wedemeyer, Eike Steinmann
Nature Reviews Gastroenterology & Hepatology.2024; 21(10): 710. CrossRef
Structural aspects of hepatitis E virus
Florencia Cancela, Ofelia Noceti, Juan Arbiza, Santiago Mirazo
Archives of Virology.2022; 167(12): 2457. CrossRef
Host Innate Immunity Against Hepatitis Viruses and Viral Immune Evasion
Chonghui Xu, Jizheng Chen, Xinwen Chen
Frontiers in Microbiology.2021;[Epub] CrossRef
A Promising Vaccination Strategy against COVID-19 on the Horizon: Heterologous Immunization
Sameer-ul-Salam Mattoo, Jinjong Myoung
Journal of Microbiology and Biotechnology.2021; 31(12): 1601. CrossRef
Hepatitis E Virus: How It Escapes Host Innate Immunity
Sébastien Lhomme, Marion Migueres, Florence Abravanel, Olivier Marion, Nassim Kamar, Jacques Izopet
Vaccines.2020; 8(3): 422. CrossRef
Chikungunya Virus nsP2 Impairs MDA5/RIG-I-Mediated Induction of NF-κB Promoter Activation: A Potential Target for Virus-Specific Therapeutics
Sojung Bae, Jeong Yoon Lee, Jinjong Myoung
Journal of Microbiology and Biotechnology.2020; 30(12): 1801. CrossRef
Zika Virus-Encoded NS2A and NS4A Strongly Downregulate NF-κB Promoter Activity
Jeong Yoon Lee, Thi Thuy Ngan Nguyen, Jinjong Myoung
Journal of Microbiology and Biotechnology.2020; 30(11): 1651. CrossRef

Middle East respiratory syndrome coronavirus-encoded ORF8b strongly antagonizes IFN-β promoter activation: its implication for vaccine design: Jeong Yoon Lee , Sojung Bae , Jinjong Myoung; J. Microbiol. 2019;57(9):803-811. Published online August 27, 2019; DOI: https://doi.org/10.1007/s12275-019-9272-7

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Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a causative agent of severe-to-fatal pneumonia especially in patients with pre-existing conditions, such as smoking and chronic obstructive pulmonary disease (COPD). MERS-CoV transmission continues to be reported in the Saudi Arabian Peninsula since its discovery in 2012. However, it has rarely been epidemic outside the area except one large outbreak in South Korea in May 2015. The genome of the epidemic MERS-CoV isolated from a Korean patient revealed its homology to previously reported strains. MERS-CoV encodes 5 accessory proteins and generally, they do not participate in the genome transcription and replication but rather are involved in viral evasion of the host innate immune responses. Here we report that ORF8b, an accessory protein of MERSCoV, strongly inhibits both MDA5- and RIG-I-mediated activation of interferon beta promoter activity while downstream signaling molecules were left largely unaffected. Of note, MDA5 protein levels were significantly down-regulated by ORF8b and co-expression of ORF4a and ORF4b. These novel findings will facilitate elucidation of mechanisms of virus-encoded evasion strategies, thus helping design rationale antiviral countermeasures against deadly MERS-CoV infection.

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mBio.2023;[Epub] CrossRef
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Wenxiang Xue, Chan Ding, Kun Qian, Ying Liao
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Luis Enjuanes, Isabel Sola, Sonia Zúñiga, José M. Honrubia, Melissa Bello-Pérez, Alejandro Sanz-Bravo, Ezequiel González-Miranda, Jesús Hurtado-Tamayo, Ricardo Requena-Platek, Li Wang, Diego Muñoz-Santos, Carlos M. Sánchez, Ana Esteban, Jorge Ripoll-Gómez
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The N-Terminal Region of Middle East Respiratory Syndrome Coronavirus Accessory Protein 8b Is Essential for Enhanced Virulence of an Attenuated Murine Coronavirus
Yuming Li, Yingkang Jin, Lijun Kuang, Zhenhua Luo, Fang Li, Jing Sun, Airu Zhu, Zhen Zhuang, Yanqun Wang, Liyan Wen, Donglan Liu, Chunke Chen, Mian Gan, Jingxian Zhao, Jincun Zhao, Tom Gallagher
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Sameer-ul-Salam Mattoo, Seong-Jun Kim, Dae-Gyun Ahn, Jinjong Myoung
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Middle East Respiratory Syndrome Coronavirus ORF8b Accessory Protein Suppresses Type I IFN Expression by Impeding HSP70-Dependent Activation of IRF3 Kinase IKKε
Lok-Yin Roy Wong, Zi-Wei Ye, Pak-Yin Lui, Xuyang Zheng, Shuofeng Yuan, Lin Zhu, Sin-Yee Fung, Kit-San Yuen, Kam-Leung Siu, Man-Lung Yeung, Zongwei Cai, Patrick Chiu-Yat Woo, Kwok-Yung Yuen, Chi-Ping Chan, Dong-Yan Jin
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Zika Virus-Encoded NS2A and NS4A Strongly Downregulate NF-κB Promoter Activity
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Chikungunya Virus nsP2 Impairs MDA5/RIG-I-Mediated Induction of NF-κB Promoter Activation: A Potential Target for Virus-Specific Therapeutics
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Nonstructural proteins NS7b and NS8 are likely to be phylogenetically associated with evolution of 2019-nCoV
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Infection, Genetics and Evolution.2020; 81: 104272. CrossRef
Methyltransferase of a cell culture-adapted hepatitis E inhibits the MDA5 receptor signaling pathway
Jinjong Myoung, Jeong Yoon Lee, Kang Sang Min
Journal of Microbiology.2019; 57(12): 1126. CrossRef

Antiviral activity of Schizonepeta tenuifolia Briquet against noroviruses via induction of antiviral interferons: Yee Ching Ng , Ye Won Kim , Jeong-Su Lee , Sung Joon Lee , Moon Jung Song; J. Microbiol. 2018;56(9):683-689. Published online August 23, 2018; DOI: https://doi.org/10.1007/s12275-018-8228-7

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Abstract

Human noroviruses are the causative agents of non-bacterial gastroenteritis worldwide. The rapid onset and resolution of disease symptoms suggest that innate immune responses are critical for controlling norovirus infection; however, no effective antivirals are yet available. The present study was conducted to examine the antiviral activities of Schizonepeta tenuifolia Briquet extract (STE) against noroviruses. Treatment of human norovirus replicon-bearing HG23 cells with STE at 5 and 10 mg/ml concentrations resulted in the reduction in the viral RNA levels by 77.2% and 85.9%, respectively. STE had no cytotoxic effects on HG23 cells. Treatment of RAW 264.7 cells infected with murine norovirus 1 (MNV-1), a surrogate virus of human noroviruses, with STE at 10 and 20 μg/ml concentrations resulted in the reduction of viral replication by 58.5% and 84.9%, respectively. STE treatment induced the expression of mRNAs for type I and type II interferons in HG23 cells and upregulated the transcription of interferon-β in infected RAW 264.7 cells via increased phosphorylation of interferon regulatory factor 3, a critical transcription regulator for type I interferon production. These
results
suggest that STE inhibits norovirus replication through the induction of antiviral interferon production during virus replication and may serve as a candidate antiviral substance for treatment against noroviruses.

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

Hypermethylation of the interferon regulatory factor 5 promoter in Epstein-Barr virus-associated gastric carcinoma: 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; J. Microbiol. 2015;53(1):70-76. Published online January 4, 2015; DOI: https://doi.org/10.1007/s12275-014-4654-3

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Abstract

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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Human Cytomegalovirus Inhibition of Interferon Signal Transduction: Daniel M. Miller , Colleen M. Cebulla , Daniel D. Sedmak; J. Microbiol. 2000;38(4):203-208.

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Abstract: Cytomegalovirus (CMV), a beta-herpesvirus with worldwide distribution, exhibits host persistence, a distinguishing characteristic of all herpesviruses. This persistence is dependent upon restricted gene expression in infected cells as well as the ability of productively infected cells to escape from normal cell-mediated anti-viral immunosurveillance. Type I (IFN-[alpha]/[beta]) and type II (IFN-[gamma]) interferons are major components of the innate defense system against viral infection. They are potent inducers of MHC class I and II antigens and of antigen processing proteins. Additionally, IFNs mediate direct anti-viral effects through induction of effector molecules that block viral infection and replication, such as 2', 5-oligoadenylate synthetase (2, 5-OAS). IFNs function through activation of well-defined signal transduction pathways that involve phosphorylation of constituent proteins and ultimate formation of active transcription factors. Recent studies have shown that a number of diverse viruses, including CMV, EBV, HPV, mumps and Ebola, are capable of inhibiting IFN-mediated signal transduction through a variety of mechanisms. As an example, CMV infection inhibits the ability of infected cells to transcribe HLA class I and II antigens as well as the antiviral effector molecules 2, 5-OAS and MxA I. EMSA studies have shown that IFN-[alpha] and IFN-[gamma] are unable to induce complete signal transduction in the presence of CMV infection, phenomena that are associated with specific decreases in JAK1 and p48. Viral inhibition of IFN signal transduction represents a new mechanistic paradigm for increased viral survival, a paradigm predicting widespread consequences in the case of signal transduction factors common to multiple cytokine pathways.

Functional Implications in Apoptosis by Interferon Inducible Gene Product 1-8D, the Binding Protein to Adenovirus Preterminal Protein: Insil Joung , Jeffrey A. Engler; J. Microbiol. 2003;41(4):295-299.

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Abstract: Adenovirus (Ad) precursor to the terminal protein (pTP) plays an essential roles in the viral DNA replication. Ad pTP serves as a primer for the synthesis of a new DNA strand during the initiation step of replication. In addition, Ad pTP forms organized spherical replication foci on the nuclear matrix (NM) and anchors the viral genome to the NM. Here we identified the interferon inducible gene product 1-8D (Inid) as a pTP binding protein by using a two-hybrid screen of a HeLa cDNA library. Of the clones obtained in this assay, nine were identical to the Inid, a 13-kDa polypeptide that shares homology with genes 1-8U and Leu-13/9-27, most of which have little known functions. The entire open reading frame (ORF) of Inid was cloned into the tetracycline inducible expression vector in order to determine the biological functions related with adenoviral infection. When Inid was introduced to the cells along with adenoviruses, fifty to sixty percent of Ad-infected cells expressing Inid had rounded morphology, which was suggestive of apoptosis. Results from the terminal deoxynucleotidyl transferase (TdT) and DNA fragmentation assays confirmed that Inid induces apoptosis in Ad-infected or in uninfected cells. The Inid binding to pTP may target the cell for apoptotic destruction as a host defense mechanism against the viral infection.

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