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Takahisa Kouwaki, Yoshimi Fukushima, Takuji Daito, Takahiro Sanada, Naoki Yamamoto, Edin J Mifsud, Chean Ring Leong, Kyoko Tsukiyama-Kohara, Michinori Kohara, Misako Matsumoto, Tsukasa Seya, Hiroyuki Oshiumi
UNLABELLED: The innate immune system is essential for controlling viral infection. Hepatitis B virus (HBV) persistently infects human hepatocytes and causes hepatocellular carcinoma. However, the innate immune response to HBV infection in vivo remains unclear. Using a tree shrew animal model, we showed that HBV infection induced hepatic interferon (IFN)-γ expression during early infection. Our in vitro study demonstrated that hepatic NK cells produced IFN-γ in response to HBV only in the presence of hepatic F4/80(+) cells...
2016: Frontiers in Immunology
Ming-Ying Lu, Ching-I Huang, Ming-Yen Hsieh, Tusty-Juan Hsieh, Edward Hsi, Pei-Chien Tsai, Yi-Shan Tsai, Ching-Chih Lin, Meng-Hsuan Hsieh, Po-Cheng Liang, Yi-Hung Lin, Nai-Jen Hou, Ming-Lun Yeh, Chung-Feng Huang, Zu-Yau Lin, Shinn-Cherng Chen, Jee-Fu Huang, Wan-Long Chuang, Chia-Yen Dai, Ming-Lung Yu
Hepatitis C virus (HCV) can replicate in peripheral blood mononuclear cells (PBMCs), which can produce interferon to defend against virus infection. We hypothesized that dynamic gene expression in PBMCs might impact the treatment efficacy of peginterferon/ribavirin in HCV patients. PBMCs were collected at baseline, 1st week and 4th week of treatment from 27 chronic HCV-1 patients with 48-week peginterferon/ribavirin therapy (screening dataset n = 7; validation dataset n = 20). A sustained virologic response (SVR) was defined as undetectable HCV RNA throughout the 24 weeks after end-of-treatment...
August 17, 2016: Oncotarget
Katarina Znidar, Masa Bosnjak, Maja Cemazar, Loree C Heller
In several preclinical tumor models, antitumor effects occur after intratumoral electroporation, also known as electrotransfer, of plasmid DNA devoid of a therapeutic gene. In mouse melanomas, these effects are preceded by significant elevation of several proinflammatory cytokines. These observations implicate the binding and activation of intracellular DNA-specific pattern recognition receptors or DNA sensors in response to DNA electrotransfer. In tumors, IFNβ mRNA and protein levels significantly increased...
2016: Molecular Therapy. Nucleic Acids
Qian Zhang, Wenyu Gou, Xiaotong Wang, Yawen Zhang, Jun Ma, Hongliang Zhang, Ying Zhang, Hao Zhang
Tibetan chicken, unlike their lowland counterparts, exhibit specific adaptations to high-altitude conditions. The genetic mechanisms of such adaptations in highland chickens were determined by resequencing the genomes of four highland (Tibetan and Lhasa White) and four lowland (White Leghorn, Lindian, and Chahua) chicken populations. Our results showed an evident genetic admixture in Tibetan chickens, suggesting a history of introgression from lowland gene pools. Genes showing positive selection in highland populations were related to cardiovascular and respiratory system development, DNA repair, response to radiation, inflammation, and immune responses, indicating a strong adaptation to oxygen scarcity and high-intensity solar radiation...
March 2016: Genome Biology and Evolution
Hiroyuki Oshiumi, Edin J Mifsud, Takuji Daito
Recognition and degradation of viral RNA are essential for antiviral innate immune responses. Cytoplasmic viral RNA is recognized by retinoic acid-inducible gene I (RIG-I)-like receptors, which trigger type I interferon (IFN) production. Secreted type I IFN activates ubiquitously expressed type I IFN receptor and induces IFN-stimulated genes (ISGs). To suppress viral replication, several nucleases degrade viral RNA. RNase L is an ISG with endonuclease activity that degrades viral RNA, producing small RNA that activates RIG-I, resulting in the amplification of type I IFN production...
March 2016: Reviews in Medical Virology
Yuan Lu, Jilong Li, Jianlin Cheng, Dennis B Lubahn
BACKGROUND: Orphan nuclear receptor estrogen related receptor β (Esrrb or ERRβ) is well known in stem cells and early embryonic development. However, little is known about its function in cancer. METHOD: We investigated the mRNA profile alterations induced by Esrrb expression and its synthetic ligand DY131 in human prostate cancer DU145 cells via RNA-Seq analysis. RESULTS: We distinguished 67 mRNAs differentially expressed by Esrrb alone...
December 1, 2015: BMC Molecular Biology
Delphine Goubau, Annemarthe G van der Veen, Probir Chakravarty, Rongtuan Lin, Neil Rogers, Jan Rehwinkel, Safia Deddouche, Ian Rosewell, John Hiscott, Caetano Reis E Sousa
IFN-α/β allow cells to fight virus infection by inducing the expression of many genes that encode effectors of antiviral defense. One of these, the Ski2-like DExH-box helicase DDX60, was recently implicated in resistance of human cells to hepatitis C virus, as well as in induction of IFN-α/β by retinoic acid inducible gene 1-like receptors (RLRs) that detect the presence of RNA viruses in a cell-intrinsic manner. Here, we sought to investigate the role of DDX60 in IFN-α/β induction and in resistance to virus infection...
December 2015: European Journal of Immunology
Haruko Sato, Hiroyuki Oshiumi, Hiromi Takaki, Hirokazu Hikono, Tsukasa Seya
Viral RNA represents a pattern molecule that can be recognized by RNA sensors in innate immunity. Humans and mice possess cytoplasmic DNA/RNA sensors for detecting viral replication. There are a number of DEAD (Asp-Glu-Ala-Asp; DExD/H) box-type helicases in mammals, among which retinoic acid-inducible gene 1 (RIG-I) and melanoma differentiation-associated protein 5 (MDA50) are indispensable for RNA sensing; however, they are functionally supported by a number of sensors that directly bind viral RNA or replicative RNA intermediates to convey signals to RIG-I and MDA5...
October 2015: Microbiology and Immunology
Oliver Grünvogel, Katharina Esser-Nobis, Anna Reustle, Philipp Schult, Birthe Müller, Philippe Metz, Martin Trippler, Marc P Windisch, Michael Frese, Marco Binder, Oliver Fackler, Ralf Bartenschlager, Alessia Ruggieri, Volker Lohmann
UNLABELLED: All major types of interferon (IFN) efficiently inhibit hepatitis C virus (HCV) replication in vitro and in vivo. Remarkably, HCV replication is not sensitive to IFN-γ in the hepatoma cell line Huh6, despite an intact signaling pathway. We performed transcriptome analyses between Huh6 and Huh-7 cells to identify effector genes of the IFN-γ response and thereby identified the DExD/H box helicase DEAD box polypeptide 60-like (DDX60L) as a restriction factor of HCV replication...
October 2015: Journal of Virology
Hiroyuki Oshiumi, Moeko Miyashita, Masaaki Okamoto, Yuka Morioka, Masaru Okabe, Misako Matsumoto, Tsukasa Seya
RIG-I-mediated type I interferon (IFN) production and nuclease-mediated viral RNA degradation are essential for antiviral innate immune responses. DDX60 is an IFN-inducible cytoplasmic helicase. Here, we report that DDX60 is a sentinel for both RIG-I activation and viral RNA degradation. We show that DDX60 is an upstream factor of RIG-I that activates RIG-I signaling in a ligand-specific manner. DDX60 knockout attenuates RIG-I signaling and significantly reduces virus-induced type I IFN production in vivo...
May 26, 2015: Cell Reports
Christine Poitou, Claire Perret, François Mathieu, Vinh Truong, Yuna Blum, Hervé Durand, Rohia Alili, Nadjim Chelghoum, Véronique Pelloux, Judith Aron-Wisnewsky, Adriana Torcivia, Jean-Luc Bouillot, Brian W Parks, Ewa Ninio, Karine Clément, Laurence Tiret
BACKGROUND: Bariatric surgery is associated to improvements in obesity-associated comorbidities thought to be mediated by a decrease of adipose inflammation. However, the molecular mechanisms behind these beneficial effects are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed RNA-seq expression profiles in adipose tissue from 22 obese women before and 3 months after surgery. Of 15,972 detected genes, 1214 were differentially expressed after surgery at a 5% false discovery rate...
2015: PloS One
Jun Hou, Gertine van Oord, Zwier M A Groothuismink, Mark A A Claassen, Kim Kreefft, Fatiha Zaaraoui-Boutahar, Wilfred F J van IJcken, Albert D M E Osterhaus, Harry L A Janssen, Arno C Andeweg, Robert J de Knegt, Andre Boonstra
UNLABELLED: Systems biology has proven to be a powerful tool to identify reliable predictors of treatment response in chronic hepatitis C virus (HCV) infection. In the present study, we studied patients with chronic HCV infection who responded to interferon (IFN)-based therapy, as evidenced by an absence of HCV RNA at the end of treatment, and focused on two issues that have not received much attention. First, we evaluated whether specific genes or gene expression patterns in blood were able to distinguish responder patients with a viral relapse from responder patients who remained virus negative after cessation of treatment...
November 2014: Journal of Virology
Ingrid Fert, Nicolas Cagnard, Simon Glatigny, Franck Letourneur, Sébastien Jacques, Judith A Smith, Robert A Colbert, Joel D Taurog, Gilles Chiocchia, Luiza M Araujo, Maxime Breban
OBJECTIVE: In HLA-B27-transgenic rats, the development of a disorder that mimics spondyloarthritis (SpA) is highly correlated with dendritic cell (DC) dysfunction. The present study was undertaken to analyze the underlying mechanisms of this via transcriptome analysis. METHODS: Transcriptome analysis of ex vivo-purified splenic CD103+CD4+ DCs from B27-transgenic rats and control rats was performed. Transcriptional changes in selected genes were confirmed by quantitative reverse transcriptase-polymerase chain reaction...
April 2014: Arthritis & Rheumatology
Xavier Suárez-Calvet, Eduard Gallardo, Gisela Nogales-Gadea, Luis Querol, Miquel Navas, Jordi Díaz-Manera, Ricard Rojas-Garcia, Isabel Illa
We investigated the molecular mechanisms involved in the pathogenesis of three inflammatory myopathies, dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM). We performed microarray experiments(†) using microdissected pathological muscle fibres from 15 patients with these disorders and five controls. Differentially expressed candidate genes were validated by immunohistochemistry on muscle biopsies, and the altered pathways were analysed in human myotube cultures. Up-regulation of genes involved in viral and nucleic acid recognition were found in the three myopathies but not in controls...
July 2014: Journal of Pathology
Anthony Fullam, Martina Schröder
Traditional functions of DExD/H-box helicases are concerned with RNA metabolism; they have been shown to play a part in nearly every cellular process that involves RNA. On the other hand, it is accepted that DexD/H-box helicases also engage in activities that do not require helicase activity. A number of DExD/H-box helicases have been shown to be involved in anti-viral immunity. The RIG-like helicases, RIG-I, mda5 and lgp2, act as important cytosolic pattern recognition receptors for viral RNA. Detection of viral nucleic acids by the RIG-like helicases or other anti-viral pattern recognition receptors leads to the induction of type I interferons and pro-inflammatory cytokines...
August 2013: Biochimica et Biophysica Acta
Hiroyuki Oshiumi, Misako Matsumoto, Tsukasa Seya
Retinoic acid-inducible gene-I(RIG-I) is a cytoplasmic RNA helicase and a viral RNA sensor. RIG-I recognizes 5' triphosphate double-stranded RNA (dsRNA) and activates the IPS-1 adaptor molecule. The association of IPS-1 with RIG-I causes the formation of the prion-like structure of IPS-1. This structure is essential for activation of the signaling required for the induction of type I interferon (IFN), which possesses strong antiviral activity. Recent studies have revealed the novel factors involved in the RIG-I-dependent pathway...
2013: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Haijun Xiao, Liancheng Shan, Haiming Zhu, Feng Xue
Osteoporosis is the most common and serious skeletal disorder among the elderly, characterized by a low bone mineral density (BMD). Low bone mass in the elderly is highly dependent on their peak bone mass (PBM) as young adults. Circulating monocytes serve as early progenitors of osteoclasts and produce significant molecules for bone metabolism. An improved understanding of the biology and genetics of osteoclast differentiation at the pathway level is likely to be beneficial for the development of novel targeted approaches for osteoporosis...
December 2012: Molecular Medicine Reports
Bogumil Kaczkowski, Maria Rossing, Ditte K Andersen, Anita Dreher, Marya Morevati, Melissa A Visser, Ole Winther, Finn Cilius Nielsen, Bodil Norrild
The interaction between human papillomavirus (HPV) and host cells is not well understood. We investigate the early stage of HPV infections by global expression profiling in a cell model, in which HaCaT cells were transfected with HPV11, HPV16 or HPV45 genomes. We report the differential expression of genes not previously implicated in HPV biology, such as the PSG family and ANKRD1, and of genes implicated in the biology of other viruses, e.g. MX1, IFI44 and DDX60. Carcinogenesis-related genes, e.g. ABL2, MGLL and CYR61, were upregulated by high-risk HPV16 and -45...
2012: Scientific Reports
Moeko Miyashita, Hiroyuki Oshiumi, Misako Matsumoto, Tsukasa Seya
The cytoplasmic viral RNA sensors RIG-I and MDA5 are important for the production of type I interferon and other inflammatory cytokines. DDX60 is an uncharacterized DEXD/H box RNA helicase similar to Saccharomyces cerevisiae Ski2, a cofactor of RNA exosome, which is a protein complex required for the integrity of cytoplasmic RNA. Expression of DDX60 increases after viral infection, and the protein localizes at the cytoplasmic region. After viral infection, the DDX60 protein binds to endogenous RIG-I protein...
September 2011: Molecular and Cellular Biology
John W Schoggins, Sam J Wilson, Maryline Panis, Mary Y Murphy, Christopher T Jones, Paul Bieniasz, Charles M Rice
The type I interferon response protects cells against invading viral pathogens. The cellular factors that mediate this defence are the products of interferon-stimulated genes (ISGs). Although hundreds of ISGs have been identified since their discovery more than 25 years ago, only a few have been characterized with respect to antiviral activity. For most ISG products, little is known about their antiviral potential, their target specificity and their mechanisms of action. Using an overexpression screening approach, here we show that different viruses are targeted by unique sets of ISGs...
April 28, 2011: Nature
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