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https://www.readbyqxmd.com/read/28429853/molecular-cloning-of-mda5-phylogenetic-analysis-of-rig-i-like-receptors-rlrs-and-differential-gene-expression-of-rlrs-interferons-and-proinflammatory-cytokines-after-in%C3%A2-vitro-challenge-with-ipnv-isav-and-sav-in-the-salmonid-cell-line-to
#1
I-K G Nerbøvik, M A Solheim, H Ø Eggestøl, A Rønneseth, R A Jakobsen, H I Wergeland, G T Haugland
The RIG-I receptors RIG-I, MDA5 and LGP2 are involved in viral recognition, and they have different ligand specificity and recognize different viruses. Activation of RIG-I-like receptors (RLRs) leads to production of cytokines essential for antiviral immunity. In fish, most research has focused on interferons, and less is known about the production of proinflammatory cytokines during viral infections. In this study, we have cloned the full-length MDA5 sequence in Atlantic salmon, and compared it with RIG-I and LGP2...
April 21, 2017: Journal of Fish Diseases
https://www.readbyqxmd.com/read/28424327/rig-i-mavs-and-sting-signaling-promote-gut-integrity-during-irradiation-and-immune-mediated-tissue-injury
#2
Julius C Fischer, Michael Bscheider, Gabriel Eisenkolb, Chia-Ching Lin, Alexander Wintges, Vera Otten, Caroline A Lindemans, Simon Heidegger, Martina Rudelius, Sébastien Monette, Kori A Porosnicu Rodriguez, Marco Calafiore, Sophie Liebermann, Chen Liu, Stefan Lienenklaus, Siegfried Weiss, Ulrich Kalinke, Jürgen Ruland, Christian Peschel, Yusuke Shono, Melissa Docampo, Enrico Velardi, Robert R Jenq, Alan M Hanash, Jarrod A Dudakov, Tobias Haas, Marcel R M van den Brink, Hendrik Poeck
The molecular pathways that regulate the tissue repair function of type I interferon (IFN-I) during acute tissue damage are poorly understood. We describe a protective role for IFN-I and the RIG-I/MAVS signaling pathway during acute tissue damage in mice. Mice lacking mitochondrial antiviral-signaling protein (MAVS) were more sensitive to total body irradiation- and chemotherapy-induced intestinal barrier damage. These mice developed worse graft-versus-host disease (GVHD) in a preclinical model of allogeneic hematopoietic stem cell transplantation (allo-HSCT) than did wild-type mice...
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28418930/the-innate-immunity-of-guinea-pigs-against-highly-pathogenic-avian-influenza-virus-infection
#3
Kun Zhang, Wei Wei Xu, Zhaowei Zhang, Jing Liu, Jing Li, Lijuan Sun, Weiyang Sun, Peirong Jiao, Xiaoyu Sang, Zhiguang Ren, Zhijun Yu, Yuanguo Li, Na Feng, Tiecheng Wang, Hualei Wang, Songtao Yang, Yongkun Zhao, Xuemei Zhang, Peter R Wilker, WenJun Liu, Ming Liao, Hualan Chen, Yuwei Gao, Xianzhu Xia
H5N1 avian influenza viruses are a major pandemic concern. In contrast to the highly virulent phenotype of H5N1 in humans and many animal models, guinea pigs do not typically display signs of severe disease in response to H5N1 virus infection. Here, proteomic and transcriptional profiling were applied to identify host factors that account for the observed attenuation of A/Tiger/Harbin/01/2002 (H5N1) virulence in guinea pigs. RIG-I and numerous interferon stimulated genes were among host proteins with altered expression in guinea pig lungs during H5N1 infection...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418387/mitochondria-are-the-powerhouses-of-immunity
#4
REVIEW
Evanna L Mills, Beth Kelly, Luke A J O'Neill
Recent evidence indicates that mitochondria lie at the heart of immunity. Mitochondrial DNA acts as a danger-associated molecular pattern (DAMP), and the mitochondrial outer membrane is a platform for signaling molecules such as MAVS in RIG-I signaling, and for the NLRP3 inflammasome. Mitochondrial biogenesis, fusion and fission have roles in aspects of immune-cell activation. Most important, Krebs cycle intermediates such as succinate, fumarate and citrate engage in processes related to immunity and inflammation, in both innate and adaptive immune cells...
April 18, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28415826/azithromycin-augments-rhinovirus-induced-ifn%C3%AE-via-cytosolic-mda5-in-experimental-models-of-asthma-exacerbation
#5
Mandy Menzel, Hamid Akbarshahi, Ellen Tufvesson, Carl Persson, Leif Bjermer, Lena Uller
Deficient production of anti-viral interferons (IFNs) may be involved in causing viral-induced asthma exacerbations. Hence, drugs inducing lung IFN production would be warranted. Azithromycin may reduce asthma exacerbations but its modus operandi is unknown. Here, we investigated if azithromycin induces IFNβ expression in vitro in rhinovirus-infected bronchial epithelial cells from asthmatic donors and in vivo in our allergic inflammation-based mouse model of viral stimulus-induced asthma exacerbations. Azithromycin dose-dependently augmented viral-induced IFNβ expression in asthmatic, but not in healthy bronchial epithelial cells...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411239/discrimination-of-cytosolic-self-and-non-self-rna-by-rig-i-like-receptors
#6
Charlotte Laessig, Karl-Peter Hopfner
RIG-I-like receptors (RLRs) are cytosolic innate immune sensors that detect pathogenic RNA and induce a systemic antiviral response. During the last decade many studies focused on their molecular characterization and the identification of RNA agonists. Thereby it became more and more clear that RLR activation needs to be carefully regulated, since constitutive signalling or detection of endogenous RNA through loss of specificity is detrimental. Here, we review the current understanding of RLR activation and selectivity...
April 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28398495/a-histological-study-of-fulminant-type-1-diabetes-mellitus-related-to-human-cytomegalovirus-reactivation
#7
Sho Yoneda, Akihisa Imagawa, Kenji Fukui, Sae Uno, Junji Kozawa, Makoto Sakai, Toshiki Yumioka, Hiromi Iwahashi, Iichiro Shimomura
Context: Fulminant type 1 diabetes mellitus (T1DM) is thought to be partly caused by virus infection. Objective: This study investigated the mechanism of β cell destruction in fulminant T1DM after drug-induced hypersensitivity syndrome (DIHS). Methods: We determined the localization of viruses of human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV), and the expression of interferon regulatory factor 3 (IRF3) and viral receptors of Z DNA binding protein 1 (ZBP1) and retinoic acid-inducible gene I (RIG-I), together with inflammatory cells by immunohistochemistry of pancreas from an autopsy fulminant T1DM patient with DIHS or seven subjects with normal glucose tolerance who underwent pancreatectomy...
April 10, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28396670/grass-carp-laboratory-of-genetics-and-physiology-2-serves-as-a-negative-regulator-in-retinoic-acid-inducible-gene-i-and-melanoma-differentiation-associated-gene-5-mediated-antiviral-signaling-in-resting-state-and-early-stage-of-grass-carp-reovirus-infection
#8
Youliang Rao, Quanyuan Wan, Chunrong Yang, Jianguo Su
Laboratory of genetics and physiology 2 (LGP2) is a key component of RIG-I-like receptors (RLRs). However, the lack of the caspase recruitment domains (CARDs) results in its controversial functional performance as a negative or positive regulator in antiviral responses. Especially, no sufficient evidence uncovers the functional mechanisms of LGP2 in RLR signaling pathways in teleost. Here, negative regulation mechanism of LGP2 in certain situations in retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5)-mediated antiviral responses was identified in Ctenopharyngodon idella kidney cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28380403/5-triphosphate-sirna-targeting-mdr1-reverses-multi-drug-resistance-and-activates-rig-i-induced-immune-stimulatory-and-apoptotic-effects-against-human-myeloid-leukaemia-cells
#9
Dengzhe Li, Robert Peter Gale, Yanfeng Liu, Baoxia Lei, Yuan Wang, Dongmei Diao, Mei Zhang
Multi-drug resistance (MDR), immune suppression and decreased apoptosis are important causes of therapy-failure in leukaemia. Short interfering RNAs (siRNAs) down-regulate gene transcription, have sequence-independent immune-stimulatory effects and synergize with other anti-cancer therapies in some experimental models. We designed a siRNA targeting MDR1 with 5'-triphosphate ends (3p-siRNA-MDR1). Treatment of leukaemia cells with 3p-siRNA-MDR1 down-regulated MDR1 expression, reduced-drug resistance and induced immune and pro-apoptotic effects in drug-resistant HL-60/Adr and K562/Adr human leukaemia cell lines...
March 21, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28377530/topoisomerase-ii-inhibitors-induce-dna-damage-dependent-interferon-responses-circumventing-ebola-virus-immune-evasion
#10
Priya Luthra, Sebastian Aguirre, Benjamin C Yen, Colette A Pietzsch, Maria T Sanchez-Aparicio, Bersabeh Tigabu, Lorraine K Morlock, Adolfo García-Sastre, Daisy W Leung, Noelle S Williams, Ana Fernandez-Sesma, Alexander Bukreyev, Christopher F Basler
Ebola virus (EBOV) protein VP35 inhibits production of interferon alpha/beta (IFN) by blocking RIG-I-like receptor signaling pathways, thereby promoting virus replication and pathogenesis. A high-throughput screening assay, developed to identify compounds that either inhibit or bypass VP35 IFN-antagonist function, identified five DNA intercalators as reproducible hits from a library of bioactive compounds. Four, including doxorubicin and daunorubicin, are anthracycline antibiotics that inhibit topoisomerase II and are used clinically as chemotherapeutic drugs...
April 4, 2017: MBio
https://www.readbyqxmd.com/read/28377495/rig-i-antiviral-signaling-drives-interleukin-23-production-and-psoriasis-like-skin-disease
#11
Huiyuan Zhu, Fangzhou Lou, Qianqian Yin, Yuanyuan Gao, Yang Sun, Jing Bai, Zhenyao Xu, Zhaoyuan Liu, Wei Cai, Fang Ke, Lingyun Zhang, Hong Zhou, Hong Wang, Gang Wang, Xiang Chen, Hongxin Zhang, Zhugang Wang, Florent Ginhoux, Chuanjian Lu, Bing Su, Honglin Wang
Retinoic acid inducible-gene I (RIG-I) functions as one of the major sensors of RNA viruses. DDX58, which encodes the RIG-I protein, has been newly identified as a susceptibility gene in psoriasis. Here, we show that the activation of RIG-I by 5'ppp-dsRNA, its synthetic ligand, directly causes the production of IL-23 and triggers psoriasis-like skin disease in mice. Repeated injections of IL-23 to the ears failed to induce IL-23 production and a full psoriasis-like skin phenotype, in either germ-free or RIG-I-deficient mice...
April 4, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28374903/rna-sensors-of-the-innate-immune-system-and-their-detection-of-pathogens
#12
REVIEW
Nanhua Chen, Pengpeng Xia, Shuangjie Li, Tangjie Zhang, Tony T Wang, Jianzhong Zhu
The innate immune system plays a critical role in pathogen recognition and initiation of protective immune response through the recognition of pathogen associated molecular patterns (PAMPs) by its pattern recognition receptors (PRRs). Nucleic acids including RNA and DNA have been recognized as very important PAMPs of pathogens especially for viruses. RNA are the major PAMPs of RNA viruses, to which most severe disease causing viruses belong thus posing a tougher challenge to human and animal health. Therefore, the understanding of the immune biology of RNA PRRs is critical for control of pathogen infections especially for RNA virus infections...
April 4, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28338936/establishment-of-a-human-hepatocellular-cell-line-capable-of-maintaining-long-term-replication-of-hepatitis-b-virus
#13
Wan-Ling Yao, Sotaro Ikeda, Yuta Tsukamoto, Keiko Shindo, Yukie Otakaki, Main Qin, Yoshikazu Iwasawa, Fumihiko Takeuchi, Yuki Kaname, Yu-Chi Chou, Chungming Chang, Koichi Watashi, Takaji Wakita, Takeshi Noda, Hiroki Kato, Takashi Fujita
Hepatitis B virus is a virus whose replication cycle cannot be completely reproduced using cultured cell lines. Here, we report an engineered cell line capable of supporting the complete HBV life cycle. We generated HepG2 cells overexpressing HBV entry receptor human NTCP, and defective in RIG-I-like receptor signaling, by knocking down the IPS-1 adaptor molecule. The resultant NtG20.i7 cells were susceptible to HBV, and its replication was detectable at 14 days post-infection and persisted for at least 35 days with a gradual increase of HBc expression...
March 11, 2017: International Immunology
https://www.readbyqxmd.com/read/28335522/extracellular-vesicles-deliver-host-and-virus-rna-and-regulate-innate-immune-response
#14
REVIEW
Takahisa Kouwaki, Masaaki Okamoto, Hirotake Tsukamoto, Yoshimi Fukushima, Hiroyuki Oshiumi
The innate immune system plays a crucial role in controlling viral infection. Pattern recognition receptors (PRRs), such as Toll-like receptors and RIG-I-like receptors, sense viral components called pathogen-associated molecular patterns (PAMPs) and trigger signals to induce innate immune responses. Extracellular vesicles (EVs), including exosomes and microvesicles, deliver functional RNA and mediate intercellular communications. Recent studies have revealed that EVs released from virus-infected cells deliver viral RNA to dendritic cells and macrophages, thereby activating PRRs in recipient cells, which results in the expression of type I interferon and pro-inflammatory cytokines...
March 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28325765/caenorhabditis-elegans-rig-i-homolog-mediates-antiviral-rna-interference-downstream-of-dicer-dependent-biogenesis-of-viral-small-interfering-rnas
#15
Stephanie R Coffman, Jinfeng Lu, Xunyang Guo, Jing Zhong, Hongshan Jiang, Gina Broitman-Maduro, Wan-Xiang Li, Rui Lu, Morris Maduro, Shou-Wei Ding
Dicer enzymes process virus-specific double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs) to initiate specific antiviral defense by related RNA interference (RNAi) pathways in plants, insects, nematodes, and mammals. Antiviral RNAi in Caenorhabditis elegans requires Dicer-related helicase 1 (DRH-1), not found in plants and insects but highly homologous to mammalian retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), intracellular viral RNA sensors that trigger innate immunity against RNA virus infection...
March 21, 2017: MBio
https://www.readbyqxmd.com/read/28318042/beyond-sensing-rig-i-continues-to-expand-its-antiviral-effector-functions
#16
EDITORIAL
Amy El Stone, Michael Gale
No abstract text is available yet for this article.
March 20, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28303593/sb-9200-a-novel-agonist-of-innate-immunity-shows-potent-antiviral-activity-against-resistant-hcv-variants
#17
Meleri Jones, Morven E Cunningham, Peter Wing, Sampath DeSilva, Rupa Challa, Anjaneyulu Sheri, Seetharamaiyer Padmanabhan, Radhakrishnan P Iyer, Brent E Korba, Nezam Afdhal, Graham R Foster
SB 9200 is a novel, first-in-class oral modulator of innate immunity that is believed to act via the activation of the RIG-I and NOD2 pathways. SB 9200 has broad-spectrum antiviral activity against RNA viruses including hepatitis C virus (HCV), norovirus, respiratory syncytial virus and influenza and has demonstrated activity against hepatitis B virus (HBV) in vitro and in vivo. In phase I clinical trials in chronically infected HCV patients, SB 9200 has been shown to reduce HCV RNA by up to 1.9 log10 . Here, we demonstrate the antiviral activity of SB 9200 against a HCV replicon system and patient derived virus...
March 17, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28298903/apoptosis-toll-like-rig-i-like-and-nod-like-receptors-are-pathways-jointly-induced-by-diverse-respiratory-bacterial-and-viral-pathogens
#18
Isidoro Martínez, Juan C Oliveros, Isabel Cuesta, Jorge de la Barrera, Vicente Ausina, Cristina Casals, Alba de Lorenzo, Ernesto García, Belén García-Fojeda, Junkal Garmendia, Mar González-Nicolau, Alicia Lacoma, Margarita Menéndez, David Moranta, Amelia Nieto, Juan Ortín, Alicia Pérez-González, Cristina Prat, Elisa Ramos-Sevillano, Verónica Regueiro, Ariel Rodriguez-Frandsen, Dolores Solís, José Yuste, José A Bengoechea, José A Melero
Lower respiratory tract infections are among the top five leading causes of human death. Fighting these infections is therefore a world health priority. Searching for induced alterations in host gene expression shared by several relevant respiratory pathogens represents an alternative to identify new targets for wide-range host-oriented therapeutics. With this aim, alveolar macrophages were independently infected with three unrelated bacterial (Streptococcus pneumoniae, Klebsiella pneumoniae, and Staphylococcus aureus) and two dissimilar viral (respiratory syncytial virus and influenza A virus) respiratory pathogens, all of them highly relevant for human health...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28295214/negative-regulators-of-the-rig-i-like-receptor-signaling-pathway
#19
REVIEW
Kendra M Quicke, Michael S Diamond, Mehul S Suthar
Upon recognition of specific molecular patterns on microbes, host cells trigger an innate immune response, which culminates in the production of type I interferons (IFNs), pro-inflammatory cytokines and chemokines, and restricts pathogen replication and spread within the host. At each stage of this response, there are stimulatory and inhibitory signals that regulate the magnitude, quality, and character of the response. Positive regulation promotes an antiviral state to control and eventually clear infection, whereas negative regulation dampens inflammation and prevents immune-mediated tissue damage...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28295207/human-gestation-associated-tissues-express-functional-cytosolic-nucleic-acid-sensing-pattern-recognition-receptors
#20
A H Bryant, G E Menzies, L M Scott, S Spencer-Harty, L B Davies, R A Smith, R H Jones, C A Thornton
The role of viral infections in adverse pregnancy outcomes has gained interest in recent years. Innate immune pattern recognition receptors (PRRs) and their signalling pathways, that yield a cytokine output in response to pathogenic stimuli, have been postulated to link infection at the maternal-fetal interface and adverse pregnancy outcomes. The objective of this study was to investigate the expression and functional response of nucleic acid ligand responsive Toll-like receptors (TLR-3, -7, -8 and -9), and retinoic acid-inducible gene 1 (RIG-I)-like receptors [RIG-I, melanoma differentiation-associated protein 5 (MDA5) and Laboratory of Genetics and Physiology 2(LGP2)] in human term gestation-associated tissues (placenta, choriodecidua and amnion) using an explant model...
March 13, 2017: Clinical and Experimental Immunology
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