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https://www.readbyqxmd.com/read/28932081/-epigallocatechin-3-gallate-enhances-poly-i-c-induced-interferon-%C3%AE-1-production-and-inhibits-hepatitis-c-virus-replication-in-hepatocytes
#1
Yi-Zhong Wang, Jie-Liang Li, Xu Wang, Ting Zhang, Wen-Zhe Ho
AIM: To investigate the effect of (-)-epigallocatechin-3-gallate (EGCG) on polyinosinic-polycytidylic acid (poly I:C)-triggered intracellular innate immunity against hepatitis C virus (HCV) in hepatocytes. METHODS: A cell culture model of HCV infection was generated by infecting a hepatoma cell line, Huh7, with HCV JFH-1 strain (JFH-1-Huh7). Poly I:C with a high molecular weight and EGCG were used to stimulate the JFH-1-Huh7 cells. Real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of intracellular mRNAs and of intracellular and extracellular HCV RNA...
August 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28931677/structurally-guided-removal-of-deisgylase-biochemical-activity-from-papain-like-protease-originating-from-the-middle-east-respiratory-syndrome-virus
#2
Courtney M Daczkowski, Octavia Goodwin, John V Dzimianski, Jonathan J Farhat, Scott D Pegan
Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging human pathogen that is the causative agent for Middle East respiratory syndrome (MERS). With MERS outbreaks resulting in over 35% fatalities and now spread to 27 countries, MERS-CoV poses a significant on-going threat to global human health. As part of its viral genome, MERS-CoV encodes for a papain-like protease (PLpro) that has been observed to act as a deubiquitinase and deISGylase to antagonize IFN-I immune pathways. This activity is in addition to its viral polypeptide cleavage function...
September 20, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28923706/specific-interferon-tau-gene-regulation-networks-in-bovine-endometrial-luminal-epithelial-cells
#3
Gan Zhao, Kangfeng Jiang, Tao Zhang, Haichong Wu, Changwei Qiu, Ganzhen Deng
Interferon tau (IFNT) plays a critical role as a pregnancy recognition factor in early pregnancy by regulating uterine epithelial gene expression. Illuminating the relation between IFNT and pregnancy will contribute significantly to early pregnancy research in ruminants. Therefore, in this study, we treated primary bovine endometrial luminal epithelial cells (bELECs) without or with IFNT (200 ng/mL) for 6 or12 h. Subsequently, RNA sequencing (RNA-seq) technology was used to evaluate differences in gene expression...
September 8, 2017: Theriogenology
https://www.readbyqxmd.com/read/28912426/deconvolution-of-dna-methylation-identifies-differentially-methylated-gene-regions-on-1p36-across-breast-cancer-subtypes
#4
Alexander J Titus, Gregory P Way, Kevin C Johnson, Brock C Christensen
Breast cancer is a complex disease consisting of four distinct molecular subtypes. DNA methylation-based (DNAm) studies in tumors are complicated further by disease heterogeneity. In the present study, we compared DNAm in breast tumors with normal-adjacent breast samples from The Cancer Genome Atlas (TCGA). We constructed models stratified by tumor stage and PAM50 molecular subtype and performed cell-type reference-free deconvolution to control for cellular heterogeneity. We identified nineteen differentially methylated gene regions (DMGRs) in early stage tumors across eleven genes (AGRN, C1orf170, FAM41C, FLJ39609, HES4, ISG15, KLHL17, NOC2L, PLEKHN1, SAMD11, WASH5P)...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28881486/how-usp18-deals-with-isg15-modified-proteins-structural-basis-for-the-specificity-of-the-protease
#5
REVIEW
Anja Basters, Klaus-Peter Knobeloch, Günter Fritz
The Ubiquitin-specific protease 18 (USP18) has two major functions: (i) it is a highly specific protease that cleaves the ubiquitin-like modifier ISG15 (interferon stimulated gene 15 kDa) from proteins, and (ii) independent from its enzymatic activity USP18 interacts with the type I interferon receptor and shuts off downstream signaling. The structures of USP18 and a USP18-ISG15 complex revealed the molecular basis of the unique specificity of the protease and might shed some light into its interaction with the interferon receptor...
September 7, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28877473/crimean-congo-hemorrhagic-fever-virus-suppresses-innate-immune-responses-via-a-ubiquitin-and-isg15-specific-protease
#6
Florine E M Scholte, Marko Zivcec, John V Dzimianski, Michelle K Deaton, Jessica R Spengler, Stephen R Welch, Stuart T Nichol, Scott D Pegan, Christina F Spiropoulou, Éric Bergeron
Antiviral responses are regulated by conjugation of ubiquitin (Ub) and interferon-stimulated gene 15 (ISG15) to proteins. Certain classes of viruses encode Ub- or ISG15-specific proteases belonging to the ovarian tumor (OTU) superfamily. Their activity is thought to suppress cellular immune responses, but studies demonstrating the function of viral OTU proteases during infection are lacking. Crimean-Congo hemorrhagic fever virus (CCHFV, family Nairoviridae) is a highly pathogenic human virus that encodes an OTU with both deubiquitinase and deISGylase activity as part of the viral RNA polymerase...
September 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28870857/molecular-characterization-and-expression-analysis-of-interferon-gamma-in-black-seabream-acanthopagrus-schlegelii
#7
Yangxi Xiang, Wei Liu, Peng Jia, Yunlong Li, Yilin Jin, Limin Chen, Jing Zhang, Kuntong Jia, Meisheng Yi
Interferon gamma (IFN-γ) is a major component in immunological signaling and plays a key role in resisting viral infection. In this study, we identified and characterized an IFN-γ gene (AsIFN-γ) in the marine fish black seabream (Acanthopagrus schlegelii). We cloned AsIFN-γ genomic sequence, which comprises four exons, three introns and an upstream promoter including several conserved regulatory elements. The complete cDNA of AsIFN-γ was 816 bp in length and encoded a putative 194 amino acids (aa) protein with a 22 aa signal peptide, six α-helices and one nuclear localization signal (NLS)...
September 7, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28869524/hpv16-e6-and-e7-upregulate-interferon-induced-antiviral-response-genes-isg15-and-ifit1-in-human-trophoblast-cells
#8
Lea M M Ambühl, Annemarie B Villadsen, Ulrik Baandrup, Karen Dybkær, Suzette Sørensen
Human papillomavirus (HPV) is suggested to infect trophoblasts in the placenta, and HPV infections are reported to be more prevalent in pregnancies with adverse outcomes. Results are however controversial, and studies investigating the molecular consequences of placental HPV infections are lacking. We studied HPV DNA localization in the placenta in cases of spontaneous abortion/spontaneous preterm delivery as well as in elective abortion/normal full-term delivery. Using in vitro assays, we investigated downstream effects of HPV16 E6 and E7 expression in trophoblast cells at the gene expression level in order to gain increased biological insight into the interaction between HPV and the cellular host...
September 3, 2017: Pathogens
https://www.readbyqxmd.com/read/28869005/human-interactome-of-the-influenza-b-virus-ns1-protein
#9
Corinna Patzina, Catherine H Botting, Adolfo García-Sastre, Richard E Randall, Benjamin G Hale
NS1 proteins of influenza A and B viruses share limited sequence homology, yet both are potent manipulators of host cell processes, particularly interferon (IFN) induction. Although many cellular partners are reported for A/NS1, only a few (e.g. PKR and ISG15) have been identified for B/NS1. Here, affinity-purification and mass spectrometry were used to expand the known host interactome of B/NS1. We identified 22 human proteins as new putative targets for B/NS1, validating several, including DHX9, ILF3, YBX1 and HNRNPC...
September 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28860075/cpg-odn-1668-induce-innate-and-adaptive-immune-responses-in-rock-bream-oplegnathus-fasciatus-against-rock-bream-iridovirus-rbiv-infection
#10
Myung-Hwa Jung, Sung-Ju Jung
Rock bream iridovirus (RBIV) causes severe mass mortalities in rock bream in Korea. CpG ODN 1668 showed promise as immunoprotective agents against RBIV infection in rock bream. In this study, we assessed innate/adaptive-related gene expression patterns in RBIV-infected rock bream with and without CpG ODN 1668 administration to determine important immune defense related factors that may affect fish survival. In the CpG ODN 1668+virus-injected group, virus copies were more than 7.4- to 790591-fold lower than in the virus-injected group at 4 d (8...
August 30, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28852929/n-pro-his49-and-e-rns-lys412-mutations-in-pig-bovine-viral-diarrhea-virus-type-2-synergistically-enhance-the-cellular-antiviral-response
#11
Jie Tao, Benqiang Li, Jinghua Chen, Chunling Zhang, Yufei Ma, Guoqiang Zhu, Huili Liu
Type I interferons are major components of the innate immune response of hosts, and accordingly, many viruses have evolved mechanisms to modulate the host response during infection. Bovine viral diarrhea virus (BVDV) nonstructural protein N(pro) and structural protein E(rns) play important roles in inhibiting type I interferon. The aim of this study was to explore the epistatic effects of amino acid mutations in N(pro) and E(rns) in porcine ST cells to characterize the immune response induced by BVDV-2. Plasmids with mutant amino acids His49 (H49), Glu22 (E22) in N(pro), and His300 (H300), Lys412 (K412) in E(rns) which had been changed to Alanine (A) had similar effects on type I interferon production in MDBK and ST cells, but resulted in much greater ISG15, OAS, and Mx production in ST cells...
August 29, 2017: Virus Genes
https://www.readbyqxmd.com/read/28842471/isgylation-a-key-to-lock-the-cell-gates-for-preventing-the-spread-of-threats
#12
REVIEW
Carolina Villarroya-Beltri, Susana Guerra, Francisco Sánchez-Madrid
Interferon stimulated gene 15 (ISG15) is an ubiquitin-like protein whose expression and conjugation to targets (ISGylation) is induced by infection, interferon (IFN)-α and -β, ischemia, DNA damage and aging. Attention has historically focused on the antiviral effects of ISGylation, which blocks the entry, replication or release of different intracellular pathogens. However, recently, new functions of ISGylation have emerged that implicate it in multiple cellular processes, such as DNA repair, autophagy, protein translation and exosome secretion...
September 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28830352/jak-inhibitor-has-the-amelioration-effect-in-lupus-prone-mice-the-involvement-of-ifn-signature-gene-downregulation
#13
Keigo Ikeda, Kunihiro Hayakawa, Maki Fujishiro, Mikiko Kawasaki, Takuya Hirai, Hiroshi Tsushima, Tomoko Miyashita, Satoshi Suzuki, Shinji Morimoto, Naoto Tamura, Kenji Takamori, Hideoki Ogawa, Iwao Sekigawa
BACKGROUND: We previously reported that JAK-STAT-pathway mediated regulation of IFN-regulatory factor genes could play an important role in SLE pathogenesis. Here, we evaluated the efficacy of the JAK inhibitor tofacitinib (TOFA) for controlling IFN signalling via the JAK-STAT pathway and as a therapeutic for SLE. RESULTS: We treated NZB/NZW F1 mice with TOFA and assessed alterations in their disease, pathological, and immunological conditions. Gene-expression results obtained from CD4(+) T cells (SLE mice) and CD3(+) T cells (human SLE patients) were measured by DNA microarray and qRT-PCR...
August 22, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28821775/atf3-negatively-regulates-cellular-antiviral-signaling-and-autophagy-in-the-absence-of-type-i-interferons
#14
Vikas Sood, Kiran Bala Sharma, Vishal Gupta, Dhurjhoti Saha, Parashar Dhapola, Manish Sharma, Utsav Sen, Shigetaka Kitajima, Shantanu Chowdhury, Manjula Kalia, Sudhanshu Vrati
Stringent regulation of antiviral signaling and cellular autophagy is critical for the host response to virus infection. However, little is known how these cellular processes are regulated in the absence of type I interferon signaling. Here, we show that ATF3 is induced following Japanese encephalitis virus (JEV) infection, and regulates cellular antiviral and autophagy pathways in the absence of type I interferons in mouse neuronal cells. We have identified new targets of ATF3 and show that it binds to the promoter regions of Stat1, Irf9, Isg15 and Atg5 thereby inhibiting cellular antiviral signaling and autophagy...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808111/interferon-tau-promotes-cell-survival-and-inhibits-specific-luteolytic-genes-in-bovine-corpus-luteum
#15
Raghavendra Basavaraja, Emilia Przygrodzka, Bartosz Pawlinski, Zdzislaw Gajewski, Monika Marzena Kaczmarek, Rina Meidan
Interferon-tau (IFNT), a maternal recognition of pregnancy signals in domestic ruminants, suppress the release of luteolytic pulses of uterine prostaglandin F2a (PGF2a), thus extending the corpus luteum (CL) life span. We hypothesized that IFNT also exerts anti-luteolytic actions in bovine CL. To examine the direct effects of IFNT on bovine CL, luteal slices and enriched luteal endothelial cells (LECs) were utilized. We found that recombinant ovine IFNT (roIFNT) markedly elevates interferon-associated genes (STAT1, STAT2, and IRF9) and interferon-stimulated genes (ISGs: MX2, ISG15, & OAS1Y) in both models...
August 14, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28783371/retracted-molecular-characterization-and-biological-activity-of-interferon-%C3%AE-in-indian-peafowl-pavo-cristatus
#16
Hongjing Zhao, Yu Wang, Juanjuan Liu, Yizhi Shao, Jinglun Li, Hongliang Chai, Mingwei Xing
DNA and Cell Biology (DNA&CB) is officially retracting the paper by Zhao H, Wang Y, Liu J, Shao Y, Li J, Chai H, Xing M, entitled, "Molecular Characterization and Biological activity of Interferon-α in Indian Peafowl (Pavo cristatus)," [Epub ahead of print]; 2017, DOI: 10.1089/dna.2017.3798. The Editor-in-Chief of DNA&CB, Dr. Carol Shoshkes Reiss, was alerted to a discrepancy between the findings in the article by Zhao et al., and those of others, about the absence of expression of ISG15 in chickens. Dr. Reiss requested from the authors a clarification in their observations and inquired about the failure to include relevant citations in the reference section of the paper...
August 7, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28774718/isg-ylation-increases-stability-of-numerous-proteins-including-stat1-which-prevents-premature-termination-of-immune-response-in-lps-stimulated-microglia
#17
Piotr Przanowski, Stefan Loska, Dominik Cysewski, Michal Dabrowski, Bozena Kaminska
Microglia are myeloid cells in the central nervous system which maintain homeostasis and contribute to repair, but instigate neuroinflammation when are activated by infection, trauma or neurological diseases. Initiation of acute inflammatory responses could be mimicked in vitro by stimulation of microglial cultures with lipopolysaccharide (LPS). We have previously demonstrated Stat-dependent induction of the Uba7 mRNA expression in LPS stimulated microglia. Uba7 is an E1 enzyme crucial for posttranslational protein modifications...
July 31, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28766555/the-tlr9-agonist-mgn1703-triggers-a-potent-type-i-interferon-response-in-the-sigmoid-colon
#18
A R Krarup, M Abdel-Mohsen, M H Schleimann, L Vibholm, P A Engen, A Dige, B Wittig, M Schmidt, S J Green, A Naqib, A Keshavarzian, X Deng, R Olesen, A M Petersen, T Benfield, L Østergaard, T A Rasmussen, J Agnholt, J R Nyengaard, A Landay, O S Søgaard, S K Pillai, M Tolstrup, P W Denton
Toll-like receptor 9 (TLR9) agonists are being developed for treatment of colorectal and other cancers, yet the impact of these drugs on human intestines remains unknown. This, together with the fact that there are additional potential indications for TLR9 agonist therapy (e.g., autoimmune and infectious diseases), led us to investigate the impact of MGN1703 (Lefitolimod) on intestinal homeostasis and viral persistence in HIV-positive individuals. Colonic sigmoid biopsies were collected (baseline and week four) from 11 HIV+ individuals on suppressive antiretroviral therapy, who received MGN1703 (60 mg s...
August 2, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28756288/production-of-rnase-iii-knockout-auxotrophic-edwardsiella-tarda-mutant-for-delivery-of-long-double-stranded-rna-and-evaluation-of-its-immunostimulatory-potential
#19
Min Sun Kim, Seung Hyuk Choi, Jeong In Yang, Ki Hong Kim
The artificially synthesized polyinosinic-polycytidylic acid (poly IC) has been widely used to induce type I IFN responses in various vertebrates including fish. However, as poly IC is too expensive to use in aquaculture, the development of another economical long dsRNA producing method is needed to practically use long dsRNAs in aquaculture farms for the control of infectious diseases. In the present study, to produce long dsRNAs economically, we developed a novel long dsRNA production system based on the RNase III gene deleted auxotrophic mutant E...
July 26, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28753426/methyltransferase-setd2-mediated-methylation-of-stat1-is-critical-for-interferon-antiviral-activity
#20
Kun Chen, Juan Liu, Shuxun Liu, Meng Xia, Xiaomin Zhang, Dan Han, Yingming Jiang, Chunmei Wang, Xuetao Cao
Interferon-α (IFNα) signaling is essential for antiviral response via induction of IFN-stimulated genes (ISGs). Through a non-biased high-throughput RNAi screening of 711 known epigenetic modifiers in cellular models of IFNα-mediated inhibition of HBV replication, we identified methyltransferase SETD2 as a critical amplifier of IFNα-mediated antiviral immunity. Conditional knockout mice with hepatocyte-specific deletion of Setd2 exhibit enhanced HBV infection. Mechanistically, SETD2 directly mediates STAT1 methylation on lysine 525 via its methyltransferase activity, which reinforces IFN-activated STAT1 phosphorylation and antiviral cellular response...
July 27, 2017: Cell
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