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https://www.readbyqxmd.com/read/28530548/critical-role-of-rig-i-and-mda5-in-early-and-late-stages-of-tulane-virus-infection
#1
Preeti Chhabra, Priya Ranjan, Theresa Cromeans, Suryaprakash Sambhara, Jan Vinjé
Human noroviruses are a major cause of acute gastroenteritis worldwide, but the lack of a robust cell culture system or small animal model have hampered a better understanding of innate immunity against these viruses. Tulane virus (TV) is the prototype virus of a tentative new genus, Recovirus, in the family Caliciviridae. Its epidemiology and biological properties most closely resemble human norovirus. The host innate immune response to RNA virus infection primarily involves pathogen-sensing toll-like receptors (TLRs) TLR3 and TLR7 and retinoic acid-inducible gene I-like receptor RIG-I and melanoma differentiation associated gene 5 (MDA5)...
May 22, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28526571/the-antiviral-signaling-mediated-by-black-carp-mda5-is-positively-regulated-by-lgp2
#2
Ji Liu, Jun Li, Jun Xiao, Hui Chen, Liang Lu, Xu Wang, Yu Tian, Hao Feng
Melanoma differentiation-associated gene 5 (MDA5) belongs to RIG-I like receptor (RLR) family, which detects cytosolic viral RNA component in immune response. In this study, MDA5 orthologue of black carp (Mylopharyngodon piceus) has been cloned and characterized. The full-length cDNA of black carp MDA5 (bcMDA5) comprises 3244 nucleotides and the predicted bcMDA5 protein contains 984 amino acids. The constitutive transcription of bcMDA5 was extremely low in all the tested tissues, which included gill, skin, muscle, intestine, kidney, spleen, liver and heart...
May 16, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28507028/rig-i-like-receptor-triggering-by-dengue-virus-drives-dendritic-cell-immune-activation-and-th1-differentiation
#3
Joris K Sprokholt, Tanja M Kaptein, John L van Hamme, Ronald J Overmars, Sonja I Gringhuis, Teunis B H Geijtenbeek
Dengue virus (DENV) causes 400 million infections annually and is one of several viruses that can cause viral hemorrhagic fever, which is characterized by uncontrolled immune activation resulting in high fever and internal bleeding. Although the underlying mechanisms are unknown, massive cytokine secretion is thought to be involved. Dendritic cells (DCs) are the main target cells of DENV, and we investigated their role in DENV-induced cytokine production and adaptive immune responses. DENV infection induced DC maturation and secretion of IL-1β, IL-6, and TNF...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28499006/clinical-characteristics-and-change-in-the-antibody-titres-of-patients-with-anti-mda5-antibody-positive-inflammatory-myositis
#4
Yoshiyuki Abe, Masakazu Matsushita, Kurisu Tada, Ken Yamaji, Yoshinari Takasaki, Naoto Tamura
Objective.: The aim of this study was to evaluate the clinical characteristics of patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive inflammatory myositis, and the change in anti-MDA5 antibody titres before and after onset. Method.: For 105 PM/DM patients, newly diagnosed in our hospital within the period 2008-2016, serum anti-MDA5 antibody levels were measured at diagnosis and after treatment by ELISA using the MESACUP anti-MDA5 test...
May 11, 2017: Rheumatology
https://www.readbyqxmd.com/read/28490218/evaluation-of-clinical-prognostic-factors-for-interstitial-pneumonia-in-anti-mda5-antibody-positive-dermatomyositis-patients
#5
Youhei Fujiki, Takuya Kotani, Kentaro Isoda, Takaaki Ishida, Takeshi Shoda, Shuzo Yoshida, Tohru Takeuchi, Shigeki Makino
OBJECTIVES: We retrospectively investigated clinical prognostic factors for interstitial pneumonia (IP) in anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-positive dermatomyositis (DM) patients. METHODS: Subjects comprised 18 patients with anti-MDA5 Ab-positive DM-IP (9 survivors; 9 deaths). RESULTS: Initial serum albumin levels, ferritin levels, and ground-glass opacity (GGO) scores in the right middle lobes were significantly higher in the death group than in the survivor group (p = ...
May 11, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28484023/coronavirus-nonstructural-protein-15-mediates-evasion-of-dsrna-sensors-and-limits-apoptosis-in-macrophages
#6
Xufang Deng, Matthew Hackbart, Robert C Mettelman, Amornrat O'Brien, Anna M Mielech, Guanghui Yi, C Cheng Kao, Susan C Baker
Coronaviruses are positive-sense RNA viruses that generate double-stranded RNA (dsRNA) intermediates during replication, yet evade detection by host innate immune sensors. Here we report that coronavirus nonstructural protein 15 (nsp15), an endoribonuclease, is required for evasion of dsRNA sensors. We evaluated two independent nsp15 mutant mouse coronaviruses, designated N15m1 and N15m3, and found that these viruses replicated poorly and induced rapid cell death in mouse bone marrow-derived macrophages. Infection of macrophages with N15m1, which expresses an unstable nsp15, or N15m3, which expresses a catalysis-deficient nsp15, activated MDA5, PKR, and the OAS/RNase L system, resulting in an early, robust induction of type I IFN, PKR-mediated apoptosis, and RNA degradation...
May 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28483922/quantitative-micro-spectroscopic-imaging-reveals-viral-and-cellular-rna-helicase-interactions-in-live-cells
#7
M J Corby, Michael R Stoneman, Gabriel Biener, Joel D Paprocki, Rajesh Kolli, Valerica Raicu, David N Frick
Human cells detect RNA viruses through a set of helicases called RIG-I like receptors (RLRs) that initiate the interferon response via a mitochondrial signaling complex. Many RNA viruses also encode helicases, which sometimes are covalently linked to proteases that cleave signaling proteins. One unresolved question is how RLRs interact with each other and with viral proteins in cells. This study examined the interactions among the hepatitis C virus (HCV) helicase and RLR helicases in live cells with quantitative micro-spectroscopic imaging (Q-MSI), a technique that determines Forster Resonance Energy Transfer (FRET) efficiency and sub-cellular donor and acceptor concentrations...
May 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28480196/mda5-autoantibody-another-indicator-of-clinical-diversity-in-dermatomyositis
#8
REVIEW
Richard D Sontheimer
Allenbach and colleagues have recently reported for the first time the results of an intriguing study of the histopathologic, immunopathologic and gene expression differences in muscle biopsy tissue from adult dermatomyositis (DM) patients who do and do not have circulating MDA5 autoantibodies (anti-MDA5). Anti-MDA5 were originally identified in a clinically-defined subset of DM patients whose disease was expressed predominately in the skin for unusually long periods of time without accompanying muscle weakness [i...
April 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28475458/mda5-associated-neuroinflammation-and-the-singleton-merten-syndrome-two-faces-of-the-same-type-i-interferonopathy-spectrum
#9
Insa Buers, Gillian I Rice, Yanick J Crow, Frank Rutsch
In 1973, Singleton and Merten described a new syndrome in 2 female probands with aortic and cardiac valve calcifications, early loss of secondary dentition, and widened medullary cavities of the phalanges. In 1984, Aicardi and Goutières defined a phenotype resembling congenital viral infection with basal ganglia calcification and increased protein content in the cerebrospinal fluid. Between 2006 and 2012, mutations in 6 different genes were described to be associated with Aicardi-Goutières syndrome, specifically-TREX1, RNASEH2A, RNASEH2B, RNASEH2C, ADAR, and SAMHD1...
May 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28473814/avian-interferon-inducible-transmembrane-protein-family-effectively-restricts-avian-tembusu-virus-infection
#10
Shilong Chen, Long Wang, Jieying Chen, Lanlan Zhang, Song Wang, Mohsan U Goraya, Xiaojuan Chi, Yang Na, Wenhan Shao, Zhou Yang, Xiancheng Zeng, Shaoying Chen, Ji-Long Chen
Avian Tembusu virus (ATMUV) is a highly pathogenic flavivirus that causes significant economic losses to the Chinese poultry industry. Our previous experiments demonstrated that ATMUV infection effectively triggered host innate immune response through MDA5 and TLR3-dependent signaling pathways. However, little information is available on the role of interferon-stimulated genes (ISGs) in defending against ATMUV infection. In this study, we found that ATMUV infection induced robust expression of type I and type III interferon (IFNs) in duck tissues...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28469767/melatonin-protects-premature-ovarian-insufficiency-induced-by-tripterygium-glycosides-role-of-sirt1
#11
Min Ma, Xiu-Ying Chen, Bin Li, Xiao-Tian Li
Melatonin confers protective effects on premature ovarian insufficiency (POI) induced by tripterygium glycosides (TG) by reducing oxidative stress. Silent information regulator 1 (SIRT1) signaling is found to be associated with the physiology and pathology of ovary. We hypothesize that melatonin could protect POI via activating SIRT1 signaling. The aim of this study was to investigate the protective effect of melatonin on POI and elucidate its potential mechanisms. Mice were assigned to melatonin treatment with or without SIRT1 inhibitor Ex527 or melatonin receptor antagonist luzindole (Luz) and then subjected to POI...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28460448/anti-mda5-antibody-as-a-potential-diagnostic-and-prognostic-biomarker-in-patients-with-dermatomyositis
#12
Liubing Li, Qian Wang, Funing Yang, Chanyuan Wu, Si Chen, Xiaoting Wen, Chenxi Liu, Yongzhe Li
The presence of anti-MDA5 antibodies in serum represents an important biomarker in the diagnosis and prediction of prognosis for patients with idiopathic inflammatory myopathies (IIMs). Due to conflicting results that have been reported regarding the detection of anti-MDA5 antibodies, the goal of this study was to assess a potential association between the presence of anti-MDA5 antibodies and dermatomyositis/polymyositis (DM/PM), as well as the diagnostic and prognostic values of anti-MDA5 antibodies for DM/PM...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28451794/comparison-of-long-term-prognosis-and-relapse-of-dermatomyositis-complicated-with-interstitial-pneumonia-according-to-autoantibodies-anti-aminoacyl-trna-synthetase-antibodies-versus-anti-melanoma-differentiation-associated-gene-5-antibody
#13
Kentaro Isoda, Takuya Kotani, Tohru Takeuchi, Takao Kiboshi, Kenichiro Hata, Takaaki Ishida, Kenichiro Otani, Takao Kamimori, Hiroshi Fujiwara, Takeshi Shoda, Shigeki Makino
The aim of this study was to investigate long-term prognosis and relapse of dermatomyositis complicated with interstitial pneumonia (DMIP) according to anti-aminoacyl tRNA synthetase (ARS) antibodies and anti-melanoma differentiation-associated gene 5 (MDA5) antibody. This retrospective study comprised 36 patients with DMIP who were divided into the anti-ARS antibody-positive group (ARS+) (n = 12), anti MDA5 antibody-positive group (MDA5+) (n = 11), double-negative group (ARS-/MDA5-) (n = 11), and double-positive group (ARS+/MDA5+) (n = 1)...
April 27, 2017: Rheumatology International
https://www.readbyqxmd.com/read/28448848/transmissible-gastroenteritis-virus-infection-induces-nf-%C3%AE%C2%BAb-activation-through-rlr-mediated-signaling
#14
Zhen Ding, Kang An, Lilan Xie, Wei Wu, Ruoxi Zhang, Dang Wang, Ying Fang, Huanchun Chen, Shaobo Xiao, Liurong Fang
Transmissible gastroenteritis virus (TGEV) is a porcine enteric coronavirus which causes lethal severe watery diarrhea in piglets. The pathogenesis of TGEV is strongly associated with inflammation. In this study, we found that TGEV infection activates transcription factors NF-κB, IRF3 and AP-1 in a time- and dose-dependent manner in porcine kidney cells. Treatment with the NF-κB-specific inhibitor BAY11-7082 significantly decreased TGEV-induced proinflammatory cytokine production, but did not affect virus replication...
April 24, 2017: Virology
https://www.readbyqxmd.com/read/28445497/prostaglandin-e2-produced-following-infection-with-theiler-s-virus-promotes-the-pathogenesis-of-demyelinating-disease
#15
Seung Jae Kim, Young-Hee Jin, Byung S Kim
Infection of various cells with Theiler's murine encephalomyelitis virus (TMEV) activates the TLR- and melanoma differentiation-associated gene 5 (MDA5)-dependent pathways, resulting in the production of IL-1β via the activation of caspase-1 upon assembly of the node-like receptor protein 3 (NLRP3) inflammasome. The role of IL-1β in the pathogenesis of TMEV-induced demyelinating disease was previously investigated. However, the signaling effects of prostaglandin E2 (PGE2) downstream of the NLRP3 inflammasome on the immune responses to viral determinants and the pathogenesis of demyelinating disease are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28436945/adar1-controls-apoptosis-of-stressed-cells-by-inhibiting-staufen1-mediated-mrna-decay
#16
Masayuki Sakurai, Yusuke Shiromoto, Hiromitsu Ota, Chunzi Song, Andrew V Kossenkov, Jayamanna Wickramasinghe, Louise C Showe, Emmanuel Skordalakes, Hsin-Yao Tang, David W Speicher, Kazuko Nishikura
Both p150 and p110 isoforms of ADAR1 convert adenosine to inosine in double-stranded RNA (dsRNA). ADAR1p150 suppresses the dsRNA-sensing mechanism that activates MDA5-MAVS-IFN signaling in the cytoplasm. In contrast, the biological function of the ADAR1p110 isoform, which is usually located in the nucleus, is largely unknown. Here, we show that stress-activated phosphorylation of ADAR1p110 by MKK6-p38-MSK MAP kinases promotes its binding to Exportin-5 and its export from the nucleus. After translocating to the cytoplasm, ADAR1p110 suppresses apoptosis in stressed cells by protecting many antiapoptotic gene transcripts that contain 3'-untranslated-region dsRNA structures primarily comprising inverted Alu repeats...
April 24, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28432527/effects-of-agaricus-blazei-murill-polysaccharide-on-cadmium-poisoning-on-the-mda5-signaling-pathway-and-antioxidant-function-of-chicken-peripheral-blood-lymphocytes
#17
Ai Lv, Ming Ge, Xuequan Hu, Wenjing Liu, Guangxing Li, Ruili Zhang
This experimental study investigated the effect of Agaricus blazei Murill polysaccharide (ABP) on cadmium (Cd) poisoning on the melanoma differentiation-associated gene 5 (MDA5) signaling pathway and antioxidant function of peripheral blood lymphocytes (PBLs) in chickens. The experiments were divided into four groups: 7-day-old chickens with normal saline (0.2 mL single/day), Cd (140 mg/kg), ABP (30 mg/mL, 0.2 mL single/day), and Cd + ABP(140 mg/kg/day + 0.2 mL ABP). Peripheral blood was collected on the 20th, 40th, and 60th days for each group, and PBLs were separated...
April 21, 2017: Biological Trace Element Research
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
#18
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/28424289/disruption-of-mda5-mediated-innate-immune-responses-by-the-3c-proteins-of-coxsackievirus-a16-coxsackievirus-a6-and-enterovirus-d68
#19
Yajuan Rui, Jiaming Su, Hong Wang, Junliang Chang, Shaohua Wang, Wenwen Zheng, Yong Cai, Wei Wei, James T Gordy, Richard Markham, Wei Kong, Wenyan Zhang, Xiao-Fang Yu
Coxsackievirus A16 (CV-A16), A6 (CV-A6), and enterovirus D68 (EV-D68) belong to the Picornaviridae family and are major causes of hand, foot, and mouth disease (HFMD) and pediatric respiratory disease worldwide. The biological characteristics of these viruses, especially their interplay with the host innate immune system, have not been well investigated. In this study, we discovered that the 3C(pro) proteins from CV-A16, CV-A6, and EV-D68 bind MDA5 and inhibit its interaction with MAVS. Consequently, MDA5-triggered type I IFN signaling in the RLR pathway was blocked by CV-A16, CV-A6, and EV-D68 3C(pro) Furthermore, CV-A16, CV-A6, and EV-D68 3C(pro) all cleave TAK1, resulting in inhibition of NF-κB activation, a host response also critical for toll-like receptor (TLR) mediated signaling...
April 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28415826/azithromycin-augments-rhinovirus-induced-ifn%C3%AE-via-cytosolic-mda5-in-experimental-models-of-asthma-exacerbation
#20
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...
May 9, 2017: Oncotarget
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