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https://www.readbyqxmd.com/read/28346662/intravenous-immunoglobulin-contributes-to-control-anti-melanoma-differentiation-associated-protein-5-mda5-antibody-associated-dermatomyositis-with-palmar-violaceous-macules-papules
#1
H Koguchi-Yoshioka, N Okiyama, K Iwamoto, Y Matsumura, T Ogawa, S Inoue, R Watanabe, M Fujimot
Autoantibodies to melanoma differentiation-associated protein 5 (MDA5) are associated with a subset of dermatomyositis (DM) patients who have rapidly progressive interstitial lung disease (RP-ILD) with poor prognosis. Intensive immunosuppressive therapy is initiated before irreversible lung damage can occur; however, there are few lines of evidence for the treatment of RP-ILD. Here, we report 3 cases of anti-MDA5 antibody-associated DM with RP-ILD in which the patients were treated with combined modality therapy including high-dose prednisolone, tacrolimus, intravenous cyclophosphamide, and immunoglobulins (IVIG)...
March 27, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28331099/interferon-inducible-oligoadenylate-synthetase-like-protein-acts-as-an-antiviral-effector-against-classical-swine-fever-virus-via-the-mda5-mediated-type-i-interferon-signaling-pathway
#2
Lian-Feng Li, Jiahui Yu, Yuexiu Zhang, Qian Yang, Yongfeng Li, Lingkai Zhang, Jinghan Wang, Su Li, Yuzi Luo, Yuan Sun, Hua-Ji Qiu
Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), which poses a serious threat to the global pig industry. Interferons (IFNs) and IFN-stimulated genes (ISGs) play a key role in host antiviral defense. We have previously screened the porcine 2' -5' -oligoadenylate synthase-like protein (pOASL) as a potential anti-CSFV ISG using a reporter CSFV. This study aimed to clarify the underlying antiviral mechanism of pOASL against CSFV. We confirmed that CSFV replication was significantly suppressed in lentivirus-delivered, pOASL-overexpressing PK-15 cells, whereas silencing the expression of endogenous pOASL by small interfering RNAs markedly enhanced CSFV growth...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28319323/further-evidence-for-specific-ifih1-mutation-as-a-cause-of-singleton-merten-syndrome-with-phenotypic-heterogeneity
#3
Maria Pettersson, Birgitta Bergendal, Johanna Norderyd, Daniel Nilsson, Britt-Marie Anderlid, Ann Nordgren, Anna Lindstrand
Singleton-Merten syndrome (MIM 182250) is an autosomal dominant inherited disorder characterized by early onset periodontitis, root resorption, osteopenia, osteoporosis, and aortic valve or thoracic aorta calcification. The disorder can have significant intrafamilial phenotypic variability. Here, we present a mother and daughter with Singleton-Merten syndrome harboring a previously described pathogenic missense mutation, c.2465G>A p.(Arg822Gln), in IFIH1 (interferon induced with helicase C domain 1), encoding MDA5 (Melanoma Differentiation-Associated protein 5)...
March 20, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28295214/negative-regulators-of-the-rig-i-like-receptor-signaling-pathway
#4
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
#5
Aled H Bryant, Georgina E Menzies, Louis M Scott, Samantha Spencer-Harty, Lleucu B Davies, Rachel A Smith, Ruth H Jones, Catherine 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 (TLR3, 7, 8 and 9), and retinoic acid-inducible gene 1 (RIG-I)-like receptors (RIG-I, MDA5 and LGP2) in human term gestation-associated tissues (placenta, choriodecidua and amnion) using an explant model...
March 13, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28286505/mda5-induces-a-stronger-interferon-response-than-rig-i-to-gcrv-infection-through-a-mechanism-involving-the-phosphorylation-and-dimerization-of-irf3-and-irf7-in-cik-cells
#6
Quanyuan Wan, Chunrong Yang, Youliang Rao, Zhiwei Liao, Jianguo Su
Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are critical cytosolic sensors that trigger the production of interferons (IFNs). Though their recognition functions are well identified, their unique roles in the downstream signal transduction remain to be elucidated. Herein, we report the differential effect between grass carp (Ctenopharyngodon idella) MDA5 (CiMDA5) and CiRIG-I on the production of various IFNs upon grass carp reovirus (GCRV) infection in C. idella kidney (CIK) cell line...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28276156/retinoic-acid-inducible-gene-1-protein-rig1-like-receptor-pathway-is-required-for-efficient-nuclear-reprogramming
#7
Nazish Sayed, Frank Ospino, Farhan Himmati, Jieun Lee, Palas Chanda, Edward S Mocarski, John P Cooke
We have revealed a critical role for innate immune signaling in nuclear reprogramming to pluripotency, and in the nuclear reprogramming required for somatic cell transdifferentiation. Activation of innate immune signaling causes global changes in the expression and activity of epigenetic modifiers to promote epigenetic plasticity. In our previous papers, we focused on the role of toll-like receptor 3 (TLR3) in this signaling pathway. Here we define the role of another innate immunity pathway known to participate in the response to viral RNA, the retinoic acid-inducible gene 1 receptor (RIG-1)-like receptor (RLR) pathway...
March 9, 2017: Stem Cells
https://www.readbyqxmd.com/read/28250012/innate-immunity-to-rna-virus-is-regulated-by-temporal-and-reversible-sumoylation-of-rig-i-and-mda5
#8
Ming-Ming Hu, Chen-Yang Liao, Qing Yang, Xue-Qin Xie, Hong-Bing Shu
Sensing of viral RNA by the cytosolic receptors RIG-I and melanoma differentiation-associated gene 5 (MDA5) leads to innate antiviral response. How RIG-I and MDA5 are dynamically regulated in innate antiviral response is not well understood. Here, we show that TRIM38 positively regulates MDA5- and RIG-I-mediated induction of downstream genes and acts as a SUMO E3 ligase for their dynamic sumoylation at K43/K865 and K96/K888, respectively, before and after viral infection. The sumoylation of MDA5 and RIG-I suppresses their K48-linked polyubiquitination and degradation in uninfected or early-infected cells...
March 1, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28224203/nucleic-acid-sensing-pattern-recognition-receptors-in-the-development-of-colorectal-cancer-and-colitis
#9
REVIEW
Liangmei He, Yayun Chen, Yuanbing Wu, Ying Xu, Zixiang Zhang, Zhiping Liu
Colorectal cancer (CRC) is a leading cause of cancer-related deaths that is often associated with inflammation initiated by activation of pattern recognition receptors (PRRs). Nucleic acid sensing PRRs are one of the major subsets of PRRs that sense nucleic acid (DNA and RNA), mainly including some members of Toll-like receptors (TLR3, 7, 8, 9), AIM2-like receptors (AIM2, IFI16), STING, cGAS, RNA polymerase III, and DExD/H box nucleic acid helicases (such as RIG-I like receptors (RIG-I, MDA5, LPG2), DDX1, 3, 5, 7, 17, 21, 41, 60, and DHX9, 36)...
February 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28195391/rig-i-is-a-key-antiviral-interferon-stimulated-gene-against-hepatitis-e-virus-dispensable-of-interferon-production
#10
Lei Xu, Wenshi Wang, Yunlong Li, Xinying Zhou, Yuebang Yin, Yijin Wang, Robert A de Man, Luc J W van der Laan, Fen Huang, Nassim Kamar, Maikel P Peppelenbosch, Qiuwei Pan
Interferons (IFNs) are broad antiviral cytokines that exert their function by inducing the transcription of hundreds of interferon-stimulated genes (ISGs). However, little is known about the antiviral potential of these cellular effectors on hepatitis E virus (HEV) infection, the leading cause of acute hepatitis globally. In this study, we profiled the antiviral potential of a panel of important human ISGs on HEV replication in cell culture models by overexpression of individual ISG. The mechanism-of-action of the key anti-HEV ISG was further studied...
February 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28194372/mir-34b-5p-suppresses-melanoma-differentiation-associated-gene-5-mda5-signaling-pathway-to-promote-avian-leukosis-virus-subgroup-j-alv-j-infected-cells-proliferaction-and-alv-j-replication
#11
Zhenhui Li, Qingbin Luo, Haiping Xu, Ming Zheng, Bahareldin Ali Abdalla, Min Feng, Bolin Cai, Xiaocui Zhang, Qinghua Nie, Xiquan Zhang
Avian leukosis virus subgroup J (ALV-J) is an oncogenic retrovirus that has a similar replication cycle to multiple viruses and therefore can be used as a model system for viral entry into host cells. However, there are few reports on the genes or microRNAs (miRNAs) that are responsible for the replication of ALV-J. Our previous miRNA and RNA sequencing data showed that the expression of miR-34b-5p was significantly upregulated in ALV-J-infected chicken spleens compared to non-infected chicken spleens, but melanoma differentiation-associated gene 5 (MDA5) had the opposite expression pattern...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28181036/ddx50-inhibits-the-replication-of-dengue-virus-2-by-upregulating-ifn-%C3%AE-production
#12
Peijun Han, Wei Ye, Xin Lv, Hongwei Ma, Daihui Weng, Yangchao Dong, Linfeng Cheng, Hesong Chen, Liang Zhang, Zhikai Xu, Yingfeng Lei, Fanglin Zhang
Dengue virus (DENV) infects approximately 390 million people per year, and each of the four DENV serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) is capable of causing infection. At present, there is no antiviral drug available for the treatment of DENV. Several DExD/H-box helicases have been shown to be involved in the antiviral immune response or viral replication. In the present study, we investigated the role of DDX50 in DENV-2 RNA replication. Our data showed that the level of DENV-2 RNA increased in DDX50 knockdown cells during an early stage of viral infection and decreased in DDX50-overexpressing cells...
February 8, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28158275/early-endonuclease-mediated-evasion-of-rna-sensing-ensures-efficient-coronavirus-replication
#13
Eveline Kindler, Cristina Gil-Cruz, Julia Spanier, Yize Li, Jochen Wilhelm, Huib H Rabouw, Roland Züst, Mihyun Hwang, Philip V'kovski, Hanspeter Stalder, Sabrina Marti, Matthias Habjan, Luisa Cervantes-Barragan, Ruth Elliot, Nadja Karl, Christina Gaughan, Frank J M van Kuppeveld, Robert H Silverman, Markus Keller, Burkhard Ludewig, Cornelia C Bergmann, John Ziebuhr, Susan R Weiss, Ulrich Kalinke, Volker Thiel
Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28154280/an-atypical-clinical-course-of-anti-mda5-antibody-positive-interstitial-lung-disease-in-a-patient-with-three-deteriorations-in-9-years
#14
Yuki Sato, Kojiro Otsuka, Koji Tamai, Yuichiro Ono, Yasuhito Hamaguchi, Keisuke Tomii
Anti-MDA5 antibody-positive patients with clinically amyopathic dermatomyositis (CADM) are at high risk of developing rapidly progressive interstitial lung disease (ILD), which is associated with a high mortality rate. Approximately half of the patients with ILD recover; however, the long-term clinical course of these patients has not been fully reported and is not completely understood. This report describes the atypical clinical course of an anti-MDA5 antibody-positive CADM patient who experienced three deteriorations of ILD in 9 years...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28127433/fibrocellular-non-specific-interstitial-pneumonia-with-favourable-prognosis-in-clinically-amyopathic-dermatomyositis
#15
Takahiro Yoshizawa, Keishi Sugino, Kazutoshi Shibuya, Toshimasa Uekusa, Sakae Homma
We report the case of a 49-year-old man who experienced dry cough and itching eruption for 2 months. The patient had Gottoron's sign, mechanic's hand, and high levels of serum Krebs von den Lungen-6 and surfactant protein D, but was negative for anti-aminoacyl transfer RNA synthetase antibodies. High-resolution chest computed tomography revealed subpleural band-like or patchy consolidation with predominance in the bilateral lower lobe. Bronchoalveolar lavage fluid showed increased total cell counts with lymphocytosis...
September 2016: Respirology Case Reports
https://www.readbyqxmd.com/read/28109007/retinoic-acid-inducible-gene-i-rig-i-like-receptors-rlrs-in-fish-current-knowledge-and-future-perspectives
#16
REVIEW
Shan Nan Chen, Peng Fei Zou, Pin Nie
Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are found conservatively present in teleost fish. All three members, RIG-I, MDA5 and LGP2 together with the downstream molecules such as MITA, TRAF3 and TBK1 have been identified in a range of fish species. However, it is a bit unexpected that RIG-I has not been reported in fish of Acanthopterygii, and it would be important to clarify the presence and role of RIG-I gene in a broad range of taxa in Teleostei. RLRs in fish can be induced in vivo and in vitro by viral pathogens as well as synthetic double-stranded RNA (dsRNA), poly(I:C), leading to the production of type I IFNs and the expression of IFN stimulated genes (ISGs)...
January 20, 2017: Immunology
https://www.readbyqxmd.com/read/28090671/lgp2-plays-an-essential-role-in-hcv-infection-induced-interferon-responses
#17
Lei Hei, Jin Zhong
Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are cytosolic pattern recognition receptors (PRR) that detect non-self RNA and activate downstream interferon (IFN) signaling. One of the RLRs, Laboratory of genetics and physiology 2 (LGP2) was originally thought to be a negative feedback regulator in RIG-I signaling pathway, but growing evidence indicates LGP2 is one co-factor of Melanoma Differentiation-Associated protein 5 (MDA5) in MDA5-mediated IFN signaling activation. Our previous work showed that MDA5 was the major PRR to sense HCV infection in hepatocytes, but the role of LGP2 in HCV infection-induced IFN signaling has not been elucidated...
January 16, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28089977/antimelanoma-differentiation-associated-gene-5-antibody-expanding-the-clinical-spectrum-in-north-american-patients-with-dermatomyositis
#18
Siamak Moghadam-Kia, Chester V Oddis, Shinji Sato, Masataka Kuwana, Rohit Aggarwal
OBJECTIVE: To determine the clinical features associated with the antimelanoma differentiation-associated gene 5 antibody (anti-MDA5) in US patients with clinically amyopathic dermatomyositis (CADM) and classic DM. METHODS: Patients with CADM were consecutively selected from the University of Pittsburgh Myositis Database from 1985 to 2013. CADM was defined by a typical DM rash without objective muscle weakness and no or minimal abnormalities of muscle enzymes, electromyography, or muscle biopsy...
January 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28063952/transcriptome-profiling-of-spleen-provides-insights-into-the-antiviral-mechanism-in-schizothorax-prenanti-after-poly-i-c-challenge
#19
Xiaogang Du, Yunkun Li, Dong Li, Fangliang Lian, Shiyong Yang, Jiayun Wu, Hanmei Liu, Guixian Bu, Fengyan Meng, Xiaohan Cao, Xianyin Zeng, Huaiyu Zhang, Zhiyu Chen
Schizothorax prenanti (S. prenanti) is an important economical cold-water fish species in southwestern China, but it is susceptible to various pathogens infection. In order to clearly elucidate the antiviral mechanism, in this study, we have analyzed the transcriptome of S. prenanti spleen after challenge with the virus mimic, poly (I:C) (pIC), using next generation sequencing technology (RNA-seq). A total of 313 differential expressed genes (DEGs) in spleen at 12 h were obtained after pIC treatment, including 268 significantly up-regulated unigenes (fold change > 2) and 45 significantly down-regulated unigenes (fold change > 2)...
January 4, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28040421/anti-mda5-dermatomyositis-mimicking-psoriatic-arthritis
#20
Iván Cabezas-Rodríguez, Isla Morante-Bolado, Anahy Brandy-García, Rubén Queiro-Silva, Lourdes Mozo, Francisco Javier Ballina-García
Dermatomyositis causes inflammation and damage of muscle and skin, and sometimes involves internal organs, especially lung parenchyma. Patients with dermatomyositis still represent a diagnostic challenge because of the rarity of this disease and the lack of specificity of some of its cutaneous manifestations. Herein, we describe the case of a patient with dermatomyositis, initially diagnosed as psoriatic arthritis, in which the performance of anti-melanoma differentiation-associated gene 5 (MDA5) antibodies was decisive to establish a definitive diagnosis...
December 28, 2016: Reumatología Clinica
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