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https://www.readbyqxmd.com/read/28615462/posttranslational-modification-as-a-critical-determinant-of-cytoplasmic-innate-immune-recognition
#1
REVIEW
Paul J Baker, Dominic De Nardo, Fiona Moghaddas, Le Son Tran, Annabell Bachem, Tan Nguyen, Thomas Hayman, Hazel Tye, James E Vince, Sammy Bedoui, Richard L Ferrero, Seth L Masters
Cell surface innate immune receptors can directly detect a variety of extracellular pathogens to which cytoplasmic innate immune sensors are rarely exposed. Instead, within the cytoplasm, the environment is rife with cellular machinery and signaling pathways that are indirectly perturbed by pathogenic microbes to activate intracellular sensors, such as pyrin, NLRP1, NLRP3, or NLRC4. Therefore, subtle changes in key intracellular processes such as phosphorylation, ubiquitination, and other pathways leading to posttranslational protein modification are key determinants of innate immune recognition in the cytoplasm...
July 1, 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28614378/comparative-analysis-of-virus-host-interactions-caused-by-a-virulent-and-an-attenuated-duck-hepatitis-a-virus-genotype-1
#2
Xumin Ou, Sai Mao, Jingyu Cao, Anchun Cheng, Mingshu Wang, Dekang Zhu, Shun Chen, Renyong Jia, Mafeng Liu, Kunfeng Sun, Qiao Yang, Ying Wu, Xiaoyue Chen
Because of their better immunogenicity and the improved protection they afford, live attenuated vaccines derived from serial passaging in an abnormal host are widely used to protect humans or animals from certain pathogens. Here, we used a virulent and a chicken embryo-attenuated duck hepatitis A virus genotype 1 to compare the different regulated immune responses induced by viruses with differing virulence. In this study, the attenuated strains had lower protein expression levels than the virulent strains as identified by immunohistochemistry...
2017: PloS One
https://www.readbyqxmd.com/read/28606988/recurrent-rhinovirus-infections-in-a-child-with-inherited-mda5-deficiency
#3
Ian T Lamborn, Huie Jing, Yu Zhang, Scott B Drutman, Jordan K Abbott, Shirin Munir, Sangeeta Bade, Heardley M Murdock, Celia P Santos, Linda G Brock, Evan Masutani, Emmanuel Y Fordjour, Joshua J McElwee, Jason D Hughes, Dave P Nichols, Aziz Belkadi, Andrew J Oler, Corinne S Happel, Helen F Matthews, Laurent Abel, Peter L Collins, Kanta Subbarao, Erwin W Gelfand, Michael J Ciancanelli, Jean-Laurent Casanova, Helen C Su
MDA5 is a cytosolic sensor of double-stranded RNA (ds)RNA including viral byproducts and intermediates. We studied a child with life-threatening, recurrent respiratory tract infections, caused by viruses including human rhinovirus (HRV), influenza virus, and respiratory syncytial virus (RSV). We identified in her a homozygous missense mutation in IFIH1 that encodes MDA5. Mutant MDA5 was expressed but did not recognize the synthetic MDA5 agonist/(ds)RNA mimic polyinosinic-polycytidylic acid. When overexpressed, mutant MDA5 failed to drive luciferase activity from the IFNB1 promoter or promoters containing ISRE or NF-κB sequence motifs...
June 12, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28605144/musculoskeletal-disease-in-mda5-related-type-i-interferonopathy-a-mendelian-mimic-of-jaccoud-s-arthropathy
#4
Luciana Martins de Carvalho, Gonza Ngoumou, Ji Woo Park, Nadja Ehmke, Nikolaus Deigendesch, Naoki Kitabayashi, Isabelle Melki, Flávio Falcäo L Souza, Andreas Tzschach, Marcello H Nogueira-Barbosa, Virgínia Ferriani, Paulo Louzada-Junior, Wilson Marques Junior, Charles M Lourenço, Prof Denise Horn, Tilmann Kallinich, Werner Stenzel, Sun Hur, Gillian I Rice, Yanick J Crow
Objectives To define the molecular basis of a multisystem phenotype with progressive musculoskeletal disease of the hands and feet including camptodactyly, subluxation and tendon rupture reminiscent of Jaccoud's arthropathy. Methods We ascertained two families segregating an autosomal dominant phenotype encompassing musculoskeletal disease and variable additional features including psoriasis, dental abnormalities, cardiac valve involvement, glaucoma and basal ganglia calcification. We measured the expression of interferon-stimulated genes in peripheral blood and skin, and undertook targeted Sanger sequencing of the IFIH1 gene encoding the cytosolic double-stranded RNA sensor MDA5...
June 12, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28594402/arrdc4-regulates-enterovirus-71-induced-innate-immune-response-by-promoting-k63-polyubiquitination-of-mda5-through-trim65
#5
Jun Meng, Zhenyu Yao, Yaqing He, Renli Zhang, Yanwei Zhang, Xiangjie Yao, Hong Yang, Long Chen, Zhen Zhang, Hailong Zhang, Xueqin Bao, Gang Hu, Tangchun Wu, Jinquan Cheng
Enterovirus 71 (EV71) is the main causative agent of hand, foot and mouth disease (HFMD), which induces significantly elevated levels of cytokines and chemokines, leading to local or system inflammation and severe complications, whereas the underlying regulatory mechanisms and the inflammatory pathogenesis remain elusive. ARRDC4 is one member of arrestins family, having important roles in glucose metabolism and G-protein-coupled receptors (GPCRs) related physiological and pathological processes, however, the function of ARRDC4 in innate immune system is largely unknown...
June 8, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28591694/the-nucleocapsid-proteins-of-mouse-hepatitis-virus-and-severe-acute-respiratory-syndrome-coronavirus-share-the-same-ifn-%C3%AE-antagonizing-mechanism-attenuation-of-pact-mediated-rig-i-mda5-activation
#6
Zhen Ding, Liurong Fang, Shuangling Yuan, Ling Zhao, Xunlei Wang, Siwen Long, Mohan Wang, Dang Wang, Mohamed Frahat Foda, Shaobo Xiao
Coronaviruses (CoVs) are a huge threat to both humans and animals and have evolved elaborate mechanisms to antagonize interferons (IFNs). Nucleocapsid (N) protein is the most abundant viral protein in CoV-infected cells, and has been identified as an innate immunity antagonist in several CoVs, including mouse hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV. However, the underlying molecular mechanism(s) remain unclear. In this study, we found that MHV N protein inhibited Sendai virus and poly(I:C)-induced IFN-β production by targeting a molecule upstream of retinoic acid-induced gene I (RIG-I) and melanoma differentiation gene 5 (MDA5)...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28580698/spontaneous-pneumomediastinum-in-a-dermatomyositis-patient-with-anti-melanoma-differentiation-associated-gene-5-antibody-and-interstitial-lung-disease-despite-an-initial-response-to-immunosuppressant
#7
Chiu Wai Shirley Chan, Ho Yin Chung, Chak Sing Lau, Helen H L Tsang
We report a 24-year-old man with anti-melanoma differentiation-associated gene-5 (MDA5) antibody-positive dermatomyositis (DM) and interstitial lung disease (ILD) who developed spontaneous pneumomediastinum. By comparing serial thoracic high-resolution computed tomography scans, we demonstrated the distinct time course showing a paradoxical occurrence of pneumomediastinum despite a radiological improvement of ILD. Our case shows that pneumomediastinum in DM can occur regardless of associated ILD and it is a serious complication that should be considered in DM patients presenting with pulmonary manifestations...
June 4, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28566605/dermatomyositis-with-rapidly-progressive-interstitial-lung-disease-treated-with-rituximab-a-report-of-3-cases-in-japan
#8
Kenichiro Tokunaga, Noboru Hagino
We performed a retrospective chart review of three patients with hypomyopathic dermatomyositis and rapidly progressive interstitial lung disease. The patients were Japanese women of 71, 69, and 65 years of age. Two patients were anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive and 1 was anti-aminoacyl-tRNA synthetase (anti-ARS) antibody-positive. Their respiratory statuses deteriorated despite the administration of glucocorticoid, calcineurin inhibitors, and intravenous cyclophosphamide therapy...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28560754/oncostatin-m-induces-rig-i-and-mda5-expression-and-enhances-the-double-stranded-rna-response-in-fibroblasts
#9
Sabine Hergovits, Christine Mais, Claude Haan, Ana P Costa-Pereira, Heike M Hermanns
Interleukin (IL)-6-type cytokines have no direct antiviral activity; nevertheless, they display immune-modulatory functions. Oncostatin M (OSM), a member of the IL-6 family, has recently been shown to induce a distinct number of classical interferon stimulated genes (ISG). Most of them are involved in antigen processing and presentation. However, induction of retinoic acid-inducible gene (RIG)-I-like receptors (RLR) has not been investigated. Here we report that OSM has the capability to induce the expression of the DExD/H-Box RNA helicases RIG-I and melanoma differentiation antigen 5 (MDA5) as well as of the transcription factors interferon regulatory factor (IRF)1, IRF7 and IRF9 in primary fibroblasts...
May 30, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28559111/pattern-recognition-receptors-in-grass-carp-ctenopharyngodon-idella-i-organization-and-expression-analysis-of-tlrs-and-rlrs
#10
Zhiwei Liao, Quanyuan Wan, Hang Su, Changsong Wu, Jianguo Su
Pattern recognition receptors (PRRs) play indispensable roles in the immune responses against invading pathogens. In the present study, we systematically identified and characterized Toll-like receptors (TLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) as well as their adaptors in grass carp (Ctenopharyngodon idella). A comprehensive analysis of BLAST and other bioinformatics methods showed that C. idella TLR family consist of 21 members and their adaptors contain four members. Phylogenetic analyses confirmed the existence of six TLR subfamilies (TLR1, 3, 4, 5, 7 and 11 subfamily) in C...
May 27, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28558073/hepatitis-e-virus-persists-in-the-presence-of-a-type-iii-interferon-response
#11
Xin Yin, Xinlei Li, Charuta Ambardekar, Zhimin Hu, Sébastien Lhomme, Zongdi Feng
The RIG-I-like RNA helicase (RLR)-mediated interferon (IFN) response plays a pivotal role in the hepatic antiviral immunity. The hepatitis A virus (HAV) and the hepatitis C virus (HCV) counter this response by encoding a viral protease that cleaves the mitochondria antiviral signaling protein (MAVS), a common signaling adaptor for RLRs. However, a third hepatotropic RNA virus, the hepatitis E virus (HEV), does not appear to encode a functional protease yet persists in infected cells. We investigated HEV-induced IFN responses in human hepatoma cells and primary human hepatocytes...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28530548/critical-role-of-rig-i-and-mda5-in-early-and-late-stages-of-tulane-virus-infection
#12
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
#13
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
#14
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...
June 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
#15
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
#16
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
#17
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 23, 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
#18
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
#19
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
#20
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
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