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https://www.readbyqxmd.com/read/29042669/rna-editing-by-adar1-regulates-innate-and-antiviral-immune-functions-in-primary-macrophages
#1
Maria Pujantell, Eva Riveira-Muñoz, Roger Badia, Marc Castellví, Edurne Garcia-Vidal, Guillem Sirera, Teresa Puig, Cristina Ramirez, Bonaventura Clotet, José A Esté, Ester Ballana
ADAR1-dependent A-to-I editing has recently been recognized as a key process for marking dsRNA as self, therefore, preventing innate immune activation and affecting the development and resolution of immune-mediated diseases and infections. Here, we have determined the role of ADAR1 as a regulator of innate immune activation and modifier of viral susceptibility in primary myeloid and lymphoid cells. We show that ADAR1 knockdown significantly enhanced interferon, cytokine and chemokine production in primary macrophages that function as antiviral paracrine factors, rendering them resistant to HIV-1 infection...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29040318/rapid-reversal-of-innate-immune-dysregulation-in-blood-of-patients-and-livers-of-humanized-mice-with-hcv-following-daa-therapy
#2
Matthew A Burchill, Justin A Roby, Nanette Crochet, Megan Wind-Rotolo, Amy E Stone, Michael G Edwards, Rachael J Dran, Michael S Kriss, Michael Gale, Hugo R Rosen
RESULTS: First, in patients receiving two different combinations of DAAs, we found that DAAs induced not only rapid viral clearance, but also a re-setting of antiviral immune responses in the peripheral blood. Specifically, we see a rapid decline in the expression of genes associated with chronic IFN stimulation (IFIT3, USP18, IFIT1) as well as a rapid decline in genes associated with inflammation (IL1β, CXCL10, CXCL11) in the peripheral blood that precedes the complete removal of virus from the blood...
2017: PloS One
https://www.readbyqxmd.com/read/29031816/designing-immunostimulatory-double-stranded-messenger-rna-with-maintained-translational-activity-through-hybridization-with-poly-a-sequences-for-effective-vaccination
#3
Satoshi Uchida, Naoto Yoshinaga, Kayoko Yanagihara, Eiji Yuba, Kazunori Kataoka, Keiji Itaka
Messenger (m)RNA vaccines require a safe and potent immunostimulatory adjuvant. In this study, we introduced immunostimulatory properties directly into mRNA molecules by hybridizing them with complementary RNA to create highly immunogenic double stranded (ds)RNAs. These dsRNA formulations, comprised entirely of RNA, are expected to be safe and highly efficient due to antigen expression and immunostimulation occurring simultaneously in the same antigen presenting cells. In this strategy, design of dsRNA is important...
September 27, 2017: Biomaterials
https://www.readbyqxmd.com/read/29027943/low-grade-dysplastic-nodules-revealed-as-the-tipping-point-during-multistep-hepatocarcinogenesis-by-dynamic-network-biomarkers
#4
Lina Lu, Zhonglin Jiang, Yulin Dai, Luonan Chen
Hepatocellular carcinoma (HCC) is a complex disease with a multi-step carcinogenic process from preneoplastic lesions, including cirrhosis, low-grade dysplastic nodules (LGDNs), and high-grade dysplastic nodules (HGDNs) to HCC. There is only an elemental understanding of its molecular pathogenesis, for which a key problem is to identify when and how the critical transition happens during the HCC initiation period at a molecular level. In this work, for the first time, we revealed that LGDNs is the tipping point (i...
October 13, 2017: Genes
https://www.readbyqxmd.com/read/29019275/identification-of-dna-methylation-and-transcriptional-regulatory-regions-in-the-promoter-of-duck-retinoic-acid-inducible-gene-i-rig-i
#5
Y U Zhang, Yang Chen, Qi Xu, Ran Liu, Ningzhao Wu, Guohong Chen
1. The aim of this study was to identify the active control area of the duck RIG-I core promoter, to predict the binding sites of transcription factors, and to provide a theoretical basis for the study of duck RIG-I function and mechanism of regulation. 2. The promoter region of duRIG-I was obtained from Ensembl; the CpG island in the duRIG-I promoter was predicted online; and the methylation status of the duRIG-I promoter was detected by the bisulphite sequencing PCR (BSP) method. 3. There was an obvious CpG island in the duRIG-I promoter, with a total of 44 CG dinucleotides...
October 11, 2017: British Poultry Science
https://www.readbyqxmd.com/read/29018447/trim25-in-the-regulation-of-the-antiviral-innate-immunity
#6
REVIEW
María Martín-Vicente, Luz M Medrano, Salvador Resino, Adolfo García-Sastre, Isidoro Martínez
TRIM25 is an E3 ubiquitin ligase enzyme that is involved in various cellular processes, including regulation of the innate immune response against viruses. TRIM25-mediated ubiquitination of the cytosolic pattern recognition receptor RIG-I is an essential step for initiation of the intracellular antiviral response and has been thoroughly documented. In recent years, however, additional roles of TRIM25 in early innate immunity are emerging, including negative regulation of RIG-I, activation of the melanoma differentiation-associated protein 5-mitochondrial antiviral signaling protein-TRAF6 antiviral axis and modulation of p53 levels and activity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29017949/tumor-necrosis-factor-receptor-associated-factor-3-from-anodonta-woodiana-is-an-important-factor-in-bivalve-immune-response-to-pathogen-infection
#7
Fufa Qu, Zhiming Xiang, Yingli Zhou, Yanping Qin, Ziniu Yu
Tumor necrosis factor receptor-associated factor 3 (TRAF3) is a multifunctional adaptor protein in innate and acquired immune system that plays a key role in the regulation of the RIG-I-like receptor (RLR) and Toll-like receptor (TLR) signaling pathway in mammals. However, the immune function of TRAF3 homologs in freshwater mollusks is not well understood. In this study, we identified a bivalve TRAF3 gene (AwTRAF3) from Anodonta woodiana and investigated its potential roles during immune challenges. The present AwTRAF3 encoded a polypeptide of 562 amino acids with predicted molecular mass of 64...
October 7, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28986837/roles-of-arenavirus-z-protein-in-mediating-virion-budding-viral-transcription-inhibition-and-interferon-beta-suppression
#8
Junjie Shao, Yuying Liang, Hinh Ly
The smallest arenaviral protein is the zinc-finger protein (Z) that belongs to the RING finger protein family. Z serves as a main component required for virus budding from the membrane of the infected cells through self-oligomerization, a process that can be aided by the viral nucleoprotein (NP) to form the viral matrix of progeny virus particles. Z has also been shown to be essential for mediating viral transcriptional repression activity by locking the L polymerase onto the viral promoter in a catalytically inactive state, thus limiting viral replication...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986447/innate-immune-recognition-of-double-stranded-rna-triggers-increased-expression-of-nkg2d-ligands-after-virus-infection
#9
Gloria Esteso, Susana Guerra, Mar Valés-Gómez, Hugh T Reyburn
Self/non-self discrimination by the innate immune system relies on germline-encoded, non-rearranging receptors expressed by innate immune cells recognizing conserved pathogen-associated molecular patterns. The natural killer group 2D (NKG2D) receptor is a potent immune-activating receptor that binds human genome-encoded ligands, whose expression is negligible in normal tissues, but increased in stress and disease conditions for reasons that are incompletely understood. Here it is not clear how the immune system reconciles receptor binding of self-proteins with self/non-self discrimination to avoid autoreactivity...
October 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28977821/viral-inhibitions-of-pact-induced-rig-i-activation
#10
EDITORIAL
Morgan Brisse, Hinh Ly
No abstract text is available yet for this article.
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28965915/interplay-between-dengue-virus-and-toll-like-receptors-rig-i-mda5-and-micrornas-implications-for-pathogenesis
#11
REVIEW
Silvio Urcuqui-Inchima, Jesús Cabrera, Anne-Lise Haenni
A growing body of evidence has demonstrated the role of components of innate immunity, including Toll-like receptors (TLRs), the retinoic acid-inducible gene I/melanoma-differentiation factor 5 (RIG-I/MDA5) and microRNAs (miRNAs) in the recognition of dengue virus (DENV) or its components by infected cells. TLR3, TLR7/8 and RIG-I/MDA5 sense genomic RNA or dsRNA, the product of an intermediate step of DENV replication, activating intracellular pathways leading to the production of antiviral effectors, including interferon and pro-inflammatory cytokines...
September 28, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28965816/tetherin-suppresses-type-i-interferon-signaling-by-targeting-mavs-for-ndp52-mediated-selective-autophagic-degradation-in-human-cells
#12
Shouheng Jin, Shuo Tian, Man Luo, Weihong Xie, Tao Liu, Tianhao Duan, Yaoxing Wu, Jun Cui
Tetherin (BST2/CD317) is an interferon-inducible antiviral factor known for its ability to block the release of enveloped viruses from infected cells. Yet its role in type I interferon (IFN) signaling remains poorly defined. Here, we demonstrate that Tetherin is a negative regulator of RIG-I like receptor (RLR)-mediated type I IFN signaling by targeting MAVS. The induction of Tetherin by type I IFN accelerates MAVS degradation via ubiquitin-dependent selective autophagy in human cells. Moreover, Tetherin recruits E3 ubiquitin ligase MARCH8 to catalyze K27-linked ubiquitin chains on MAVS at lysine 7, which serves as a recognition signal for NDP52-dependent autophagic degradation...
September 27, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28962219/relationship-between-sex-hormones-and-rig-i-signaling-in-peripheral-blood-mononuclear-cells-of-patients-infected-with-hepatitis-c-virus
#13
Fang Ping Wang, Ping An Zhang, Xiao Yan Yang
It has previously been suggested that men and women demonstrate differing immune responses to hepatitis C virus (HCV) infection, resulting in the investigation of the role of sex hormones and if they influence the anti-HCV response. The present study aimed to examine if hormone levels were associated with interferon (IFN) signaling pathways in peripheral blood mononuclear cells of 131 patients infected with HCV and 113 healthy controls. HCV infection was diagnosed based on the presence of anti-HCV antibodies and HCV RNA in serum...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28957692/4-3h-quinazolone-regulates-innate-immune-signaling-upon-respiratory-syncytial-virus-infection-by-moderately-inhibiting-the-rig-1-pathway-in-raw264-7-cell
#14
Liwei He, Fangtian Fan, Xianbang Hou, Hongyan Wu, Juan Wang, Huiqin Xu, Yun Sun
The root of Isatis indigotica, also known as Ban-Lan-Gen (BLG), is commonly used for prevention and early treatment of respiratory virus infection, but the underlying mechanisms of action remain unclear. In the early stage of infection, the innate immune system is activated by virus, and related immune cells such as macrophages secrete large amounts of cytokines including IFNs and ILs. On the one hand, these cytokines can remove virus. On the other hand, they dominantly mediate the inflammatory injury caused by viral infection...
September 25, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28955379/rig-i-like-receptor-signaling-in-singleton-merten-syndrome
#15
REVIEW
Changming Lu, Mary MacDougall
Singleton-Merten syndrome (SMS) is an autosomal dominant, multi-system innate immune disorder characterized by early and severe aortic and valvular calcification, dental and skeletal abnormalities, psoriasis, glaucoma, and other varying clinical findings. Recently we identified a specific gain-of-function mutation in IFIH1, interferon induced with helicase C domain 1, segregated with this disease. SMS disease without hallmark dental anomalies, termed atypical SMS, has recently been reported caused by variants in DDX58, DEXD/H-box helicase 58...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28955326/influenza-a-virus-pa-antagonizes-interferon-%C3%AE-by-interacting-with-interferon-regulatory-factor-3
#16
Chenyang Yi, Zongzheng Zhao, Shengyu Wang, Xin Sun, Dan Zhang, Xiaomei Sun, Anding Zhang, Meilin Jin
The influenza A virus (IAV) can be recognized by retinoic acid-inducible gene I (RIG-I) to activate the type I interferon response and induce antiviral effects. The virus has evolved several strategies to evade the innate immune response, including non-structural protein 1 (NS1) and its polymerase subunits. The mechanism by which NS1 inhibits interferon-β (IFN-β) is well understood, whereas the mechanism by which polymerase acid protein (PA) inhibits IFN-β remains to be elucidated. In this study, we observed that the IAV PA protein could inhibit the production of IFN-β and interferon-stimulated genes induced by Sendai virus through interferon regulatory factor 3 (IRF3), but not through nuclear factor-kappaB (NF-kappaB)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28948228/stratified-ubiquitination-of-rig-i-creates-robust-immune-response-and-induces-selective-gene-expression
#17
Huifang Xian, Weihong Xie, Shuai Yang, Qingxiang Liu, Xiaojun Xia, Shouheng Jin, Tingzhe Sun, Jun Cui
The activation of retinoic acid-inducible gene I (RIG-I), an indispensable viral RNA sensor in mammals, is subtly regulated by ubiquitination. Although multiple ubiquitination sites at the amino terminus of RIG-I have been identified, their functional allocations in RIG-I activation remain elusive. We identified a stratified model for RIG-I amino-terminal ubiquitination, in which initiation at either Lys(164) or Lys(172) allows subsequent ubiquitination at other lysines, to trigger and amplify RIG-I activation...
September 2017: Science Advances
https://www.readbyqxmd.com/read/28945328/inactivated-sendai-virus-particles-upregulate-cancer-cell-icam-1-expression-with-enhancing-nk-cell-sensitivity-on-cancer-cell
#18
Simin Li, Tomoyuki Nishikawa, Yasufumi Kaneda
We have already reported that the inactivated Sendai virus (hemagglutinating virus of Japan; HVJ) envelope (HVJ-E) has multiple anti-cancer effects, including induction of cancer-selective cell death and activation of anti-cancer immunity. HVJ-E stimulates dendritic cells (DCs) to produce cytokines and chemokines such as IFN-β, IL-6, CCL5 and CXCL10, which activate both CD8(+) T cells and NK cells and recruit them to the tumor microenvironment. However, the effect of HVJ-E on modulating the sensitivity of cancer cells to immune cell attack has yet to be investigated...
September 25, 2017: Cancer Science
https://www.readbyqxmd.com/read/28940253/pbrm1-restricts-the-basal-activity-of-innate-immune-system-through-repressing-rig-i-like-receptor-signaling-and-is-a-potential-prognostic-biomarker-for-colon-cancer
#19
Xing-Sheng Shu, Yingying Zhao, Yanmei Sun, Lan Zhong, Yingduan Cheng, Yixiang Zhang, Kaile Ning, Qian Tao, Yejun Wang, Ying Ying
It has long been known that patients suffering from inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer (CRC). The innate immune system of host cells provides a first-line defence against pathogenic infection, whereas uncontrolled inflammatory response under homeostatic conditions usually leads to pathological consequences, as exemplified by the chronic inflammation of IBD. The key molecules and pathways keeping innate immunity in check are still poorly defined. Here, we report that chromatin remodeler polybromo-1 (PBRM1) is a repressor of innate immune signaling mediated by RIG-I-like receptors (RLRs)...
September 20, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28934360/pkacs-attenuate-innate-antiviral-response-by-phosphorylating-visa-and-priming-it-for-march5-mediated-degradation
#20
Bing-Ru Yan, Lu Zhou, Ming-Ming Hu, Mi Li, Heng Lin, Yan Yang, Yan-Yi Wang, Hong-Bing Shu
Sensing of viral RNA by RIG-I-like receptors initiates innate antiviral response, which is mediated by the central adaptor VISA. How the RIG-I-VISA-mediated antiviral response is terminated at the late phase of infection is enigmatic. Here we identified the protein kinase A catalytic (PKAC) subunits α and β as negative regulators of RNA virus-triggered signaling in a redundant manner. Viral infection up-regulated cellular cAMP levels and activated PKACs, which then phosphorylated VISA at T54. This phosphorylation abrogated virus-induced aggregation of VISA and primed it for K48-linked polyubiquitination and degradation by the E3 ligase MARCH5, leading to attenuation of virus-triggered induction of downstream antiviral genes...
September 2017: PLoS Pathogens
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