keyword
https://read.qxmd.com/read/34161773/riok3-inhibits-the-antiviral-immune-response-by-facilitating-trim40-mediated-rig-i-and-mda5-degradation
#21
JOURNAL ARTICLE
Yong Shen, Kejun Tang, Dongdong Chen, Mengying Hong, Fangfang Sun, SaiSai Wang, Yuehai Ke, Tingting Wu, Ren Sun, Jing Qian, Yushen Du
The type I interferon (IFN) pathway is a key component of innate immune response upon invasion of foreign pathogens. It is also under precise control to prevent excessive upregulation and undesired inflammation cascade. In the present study, we report that Riok3, an atypical kinase, negatively regulates retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) sensing-induced type I IFN signaling. Riok3 deficiency selectively inhibits RNA viral replication in vitro, resulting from an upregulated type I IFN pathway...
June 22, 2021: Cell Reports
https://read.qxmd.com/read/34093517/analysis-of-porcine-rig-i-like-receptors-revealed-the-positive-regulation-of-rig-i-and-mda5-by-lgp2
#22
JOURNAL ARTICLE
Shuangjie Li, Jie Yang, Yuanyuan Zhu, Hui Wang, Xingyu Ji, Jia Luo, Qi Shao, Yulin Xu, Xueliang Liu, Wanglong Zheng, François Meurens, Nanhua Chen, Jianzhong Zhu
The RLRs play critical roles in sensing and fighting viral infections especially RNA virus infections. Despite the extensive studies on RLRs in humans and mice, there is a lack of systemic investigation of livestock animal RLRs. In this study, we characterized the porcine RLR members RIG-I, MDA5 and LGP2. Compared with their human counterparts, porcine RIG-I and MDA5 exhibited similar signaling activity to distinct dsRNA and viruses, via similar and cooperative recognitions. Porcine LGP2, without signaling activity, was found to positively regulate porcine RIG-I and MDA5 in transfected porcine alveolar macrophages (PAMs), gene knockout PAMs and PK-15 cells...
2021: Frontiers in Immunology
https://read.qxmd.com/read/33983932/rna-editing-at-a-limited-number-of-sites-is-sufficient-to-prevent-mda5-activation-in-the-mouse-brain
#23
JOURNAL ARTICLE
Jung In Kim, Taisuke Nakahama, Ryuichiro Yamasaki, Pedro Henrique Costa Cruz, Tuangtong Vongpipatana, Maal Inoue, Nao Kanou, Yanfang Xing, Hiroyuki Todo, Toshiharu Shibuya, Yuki Kato, Yukio Kawahara
Adenosine deaminase acting on RNA 1 (ADAR1), an enzyme responsible for adenosine-to-inosine RNA editing, is composed of two isoforms: nuclear p110 and cytoplasmic p150. Deletion of Adar1 or Adar1 p150 genes in mice results in embryonic lethality with overexpression of interferon-stimulating genes (ISGs), caused by the aberrant recognition of unedited endogenous transcripts by melanoma differentiation-associated protein 5 (MDA5). However, among numerous RNA editing sites, how many RNA sites require editing, especially by ADAR1 p150, to avoid MDA5 activation and whether ADAR1 p110 contributes to this function remains elusive...
May 2021: PLoS Genetics
https://read.qxmd.com/read/33966599/lipotoxicity-reduces-ddx58-rig-1-expression-and-activity-leading-to-impaired-autophagy-and-cell-death
#24
JOURNAL ARTICLE
Karla K Frietze, Alyssa M Brown, Dividutta Das, Raymond G Franks, Jessie Lee Cunningham, Michael Hayward, Joseph T Nickels
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally. NAFLD is a consequence of fat accumulation in the liver leading to lipotoxicity. Increasing evidence has demonstrated the critical role of autophagy in NAFLD. This study uncovers the unexpected role of immune surveillance protein DDX58/Rig-1 (DExD/H box helicase 58) in activating macroautophagy/autophagy and protecting from lipotoxicity associated with NAFLD. Here we show for the first time that DDX58 protein is significantly reduced in nonalcoholic steatohepatitis (NASH) mouse model, an aggressive form of NAFLD characterized by inflammation and fibrosis of the liver...
January 2022: Autophagy
https://read.qxmd.com/read/33363525/targeting-the-histone-methyltransferase-disruptor-of-telomeric-silencing-1-like-restricts-avian-leukosis-virus-subgroup-j-replication-by-restoring-the-innate-immune-response-in-chicken-macrophages
#25
JOURNAL ARTICLE
Shihao Chen, Dedong Wang, Yinyin Liu, Ruihan Zhao, Ting Wu, Xuming Hu, Zhiming Pan, Hengmi Cui
Avian leukosis virus subgroup J (ALV-J), an oncogenic retrovirus, is known to cause immunosuppression and various types of cancer in chickens. Recent reports have shown that epigenetic changes in DNA and chromatin are widely implicated in the life cycle of diverse viruses, and reversal of these changes in host cells can lead to alterations in the propagation of viruses. In the present study, we found that disruptor of telomeric silencing 1-like (DOT1L), a histone H3 lysine79 (H3K79) methyltransferase, was upregulated during ALV-J infection in chicken macrophage HD11 cells...
2020: Frontiers in Microbiology
https://read.qxmd.com/read/33248566/avian-toll-like-receptor-3-isoforms-and-evaluation-of-toll-like-receptor-3-mediated-immune-responses-using-knockout-quail-fibroblast-cells
#26
JOURNAL ARTICLE
Mahesh Kc, John M Ngunjiri, Joonbum Lee, Jinsoo Ahn, Mohamed Elaish, Amir Ghorbani, Michael E C Abundo, Kichoon Lee, Chang-Won Lee
Toll-like receptor 3 (TLR3) induces host innate immune response on recognition of viral double-stranded RNA (dsRNA). Although several studies of avian TLR3 have been reported, none of these studies used a gene knockout (KO) model to directly assess its role in inducing the immune response and effect on other dsRNA receptors. In this study, we determined the coding sequence of quail TLR3, identified isoforms, and generated TLR3 KO quail fibroblast (QT-35) cells using a CRISPR/Cas9 system optimized for avian species...
December 2020: Poultry Science
https://read.qxmd.com/read/32560274/rig-i-plays-a-dominant-role-in-the-induction-of-transcriptional-changes-in-zika-virus-infected-cells-which-protect-from-virus-induced-cell-death
#27
JOURNAL ARTICLE
Mirjam Schilling, Anne Bridgeman, Nicki Gray, Jonny Hertzog, Philip Hublitz, Alain Kohl, Jan Rehwinkel
The Zika virus (ZIKV) has received much attention due to an alarming increase in cases of neurological disorders including congenital Zika syndrome associated with infection. To date, there is no effective treatment available. An immediate response by the innate immune system is crucial for effective control of the virus. Using CRISPR/Cas9-mediated knockouts in A549 cells, we investigated the individual contributions of the RIG-I-like receptors MDA5 and RIG-I to ZIKV sensing and control of this virus by using a Brazilian ZIKV strain...
June 16, 2020: Cells
https://read.qxmd.com/read/32425931/targeted-knockout-of-mda5-and-tlr3-in-the-df-1-chicken-fibroblast-cell-line-impairs-innate-immune-response-against-rna-ligands
#28
JOURNAL ARTICLE
Su Bin Lee, Young Hyun Park, Kelly Chungu, Seung Je Woo, Soo Taek Han, Hee Jung Choi, Deivendran Rengaraj, Jae Yong Han
The innate immune system, which senses invading pathogens, plays a critical role as the first line of host defense. After recognition of foreign RNA ligands (e.g., RNA viruses), host cells generate an innate immune or antiviral response via the interferon-mediated signaling pathway. Retinoic acid-inducible gene I (RIG-1) acts as a major sensor that recognizes a broad range of RNA ligands in mammals; however, chickens lack a RIG-1 homolog, meaning that RNA ligands should be recognized by other cellular sensors such as melanoma differentiation-associated protein 5 (MDA5) and toll-like receptors (TLRs)...
2020: Frontiers in Immunology
https://read.qxmd.com/read/32074012/endogenous-retrovirus-activation-as-a-key-mechanism-of-anti-tumor-immune-response-in-radiotherapy
#29
JOURNAL ARTICLE
Andrew K Lee, Dong Pan, Xuhui Bao, Mengjie Hu, Fang Li, Chuan-Yuan Li
The generation of DNA double-strand breaks has historically been taught as the mechanism through which radiotherapy kills cancer cells. Recently, radiation-induced cytosolic DNA release and activation of the cGAS/STING pathway, with ensuing induction of interferon secretion and immune activation, have been recognized as important mechanisms for radiation-mediated anti-tumor efficacy. Here we demonstrate that radiation-induced activation of endogenous retroviruses (ERVs) also plays a major role in regulating the anti-tumor immune response during irradiation...
April 2020: Radiation Research
https://read.qxmd.com/read/32049361/endothelial-cell-specific-deficiency-of-the-adenosine-deaminase-adar1-aggravates-lps-induced-lung-injury-in-mice-via-an-mda5-independent-pathway
#30
JOURNAL ARTICLE
Xiao-Lin Wang, Ru Yan, Zhen Zhang, Guang-Zhi Cong, Zhong-Jie Yi, Yi-Ping Leng, Alex F Chen
Adenosine deaminase acting on RNA 1 (ADAR1) has been shown to participate in the regulation of endothelial cells (ECs), as well as local and systemic inflammatory responses. Here, we find that bacterial lipopolysaccharide (LPS)-induced upregulation of ADAR1 in lung ECs is impaired in aged mice, an animal model with high rates of sepsis and mortality. Endothelial cell-specific ADAR1 knockout (ADAR1ECKO ) mice suffer from higher mortality rates, aggravated lung injury, and increased vascular permeability under LPS challenge...
February 12, 2020: FEBS Letters
https://read.qxmd.com/read/32032681/sendai-virus-v-protein-decreases-nitric-oxide-production-by-inhibiting-rig-i-signaling-in-infected-raw264-7-macrophages
#31
JOURNAL ARTICLE
Naoko Morita, Yukie Tanaka, Erdenezaya Odkhuu, Yoshikazu Naiki, Takayuki Komatsu, Naoki Koide
Sendai virus V protein is a known antagonist of RIG-I-like receptors (RLRs) RIG-I and MDA5, which activate transcription factors IRF3, leading to activation of ISGF3 and NF-κB. These transcription factors are known activators of inducible NO synthase (iNOS) and increase the production of nitric oxide (NO). By inhibiting ISGF3 and NF-κB, the V protein acts as an indirect negative regulator of iNOS and NO. Here we report that the V gene knockout Sendai virus [SeV V(-)] markedly enhanced iNOS expression and subsequent NO production in infected macrophages compared to wild-type SeV...
February 4, 2020: Microbes and Infection
https://read.qxmd.com/read/31956894/an-internal-deletion-of-adar-rescued-by-mavs-deficiency-leads-to-a-minute-phenotype
#32
JOURNAL ARTICLE
Prajakta Bajad, Florian Ebner, Fabian Amman, Brigitta Szabó, Utkarsh Kapoor, Greeshma Manjali, Alwine Hildebrandt, Michael P Janisiw, Michael F Jantsch
The RNA-editing protein ADAR is essential for early development in the mouse. Genetic evidence suggests that A to I editing marks endogenous RNAs as 'self'. Today, different Adar knockout alleles have been generated that show a common phenotype of apoptosis, liver disintegration, elevated immune response and lethality at E12.5. All the Adar knockout alleles can be rescued by a concomitant deletion of the innate immunity genes Mavs or Ifih1 (MDA5), albeit to different extents. This suggests multiple functions of ADAR...
January 20, 2020: Nucleic Acids Research
https://read.qxmd.com/read/31829086/the-rna-binding-protein-quaking-represses-host-interferon-response-by-downregulating-mavs
#33
JOURNAL ARTICLE
Kuo-Chieh Liao, Vanessa Chuo, W Samuel Fagg, Shelton S Bradrick, Julien Pompon, Mariano A Garcia-Blanco
Quaking (QKI) is an RNA-binding protein (RBP) involved in multiple aspects of RNA metabolism and many biological processes. Despite a known immune function in regulating monocyte differentiation and inflammatory responses, the degree to which QKI regulates the host interferon (IFN) response remains poorly characterized. Here we show that QKI ablation enhances poly(I:C) and viral infection-induced IFNΒ transcription. Characterization of IFN-related signaling cascades reveals that QKI knockout results in higher levels of IRF3 phosphorylation...
December 12, 2019: RNA Biology
https://read.qxmd.com/read/31565151/cd28-deficiency-ameliorates-blast-exposure-induced-lung-inflammation-oxidative-stress-apoptosis-and-t-cell-accumulation-in-the-lungs-via-the-pi3k-akt-foxo1-signaling-pathway
#34
JOURNAL ARTICLE
Yunen Liu, Changci Tong, Ying Xu, Peifang Cong, Ying Liu, Lin Shi, Xiuyun Shi, Yan Zhao, Guangyuan Bi, Hongxu Jin, Mingxiao Hou
Although CD28 is associated with the expression of inflammatory mediators, apoptosis-related protein, immunosuppression, and tumorigenesis, the effects of CD28 deficiency on blast exposure-induced lung injury have not been investigated. In this study, we have explored the effects of CD28 on blast exposure-induced lung injury and studied its potential molecular mechanisms. A mouse model of blast exposure-induced acute lung injury was established. Sixty C57BL/6 wild-type (WT) and CD28 knockout (CD28-/- ) mice were randomly divided into control or model groups...
2019: Oxidative Medicine and Cellular Longevity
https://read.qxmd.com/read/31433974/attenuation-of-the-innate-immune-response-against-viral-infection-due-to-znf598-promoted-binding-of-fat10-to-rig-i
#35
JOURNAL ARTICLE
Guanming Wang, Takahisa Kouwaki, Masaaki Okamoto, Hiroyuki Oshiumi
Excessive innate immune response is harmful to the host, and aberrant activation of the cytoplasmic viral RNA sensors RIG-I and MDA5 leads to autoimmune disorders. ZNF598 is an E3 ubiquitin ligase involved in the ribosome quality control pathway. It is also involved in the suppression of interferon (IFN)-stimulated gene (ISG) expression; however, its underlying mechanism is unclear. In this study, we show that ZNF598 is a negative regulator of the RIG-I-mediated signaling pathway, and endogenous ZNF598 protein binds to RIG-I...
August 20, 2019: Cell Reports
https://read.qxmd.com/read/30861413/knockdown-of-igf-1r-triggers-viral-rna-sensor-mda5-and-rig-i-mediated-mitochondrial-apoptosis-in-colonic-cancer-cells
#36
JOURNAL ARTICLE
Shu-Qing Wang, Xiang-Yu Yang, Xin-Feng Yu, Shu-Xiang Cui, Xian-Jun Qu
The important role of insulin-like growth factor-1 receptor (IGF-1R) in tumorigenesis has been well established. The classical model involves IGF-1R binding to IGF-1/2, the following activation of PI3K-Akt-signaling cascades, driving cell proliferation and apoptosis inhibition. Here we report a new signal transduction pathway of IGF-1R in the intestinal epithelium. Using heterozygous knockout mice (Igf1r+/- ), we analyzed the expressions of viral RNA sensors MDA5 and RIG-I in the intestinal epithelium. Igf1r+/- mice exhibited higher MDA5 and RIG-I than wild-type (WT) mice, indicating that knockdown of IGF-1R could trigger MDA5 and RIG-I...
June 7, 2019: Molecular Therapy. Nucleic Acids
https://read.qxmd.com/read/30700604/gadd45%C3%AE-activated-early-in-the-course-of-herpes-simplex-virus-1-infection-suppresses-the-activation-of-a-network-of-innate-immunity-genes
#37
JOURNAL ARTICLE
Mingmin She, Haifang Jiang, Xiaoxiang Chen, Xiaoqing Chen, Xianjie Liu, Xueyan Zhang, Bernard Roizman, Grace G Zhou
The stress response genes encoding GADD45γ, and to a lesser extent GADD45β, are activated early in infection with herpes simplex virus 1 (HSV-1). Cells that had been depleted of GADD45γ by transfection of short hairpin RNA (shRNA) or in which the gene had been knocked out (ΔGADD45γ) yielded significantly less virus than untreated infected cells. Consistent with lower virus yields, the ΔGADD45γ cells (either uninfected or infected with HSV-1) exhibited significantly higher levels of transcripts of a cluster of innate immunity genes, including those encoding IFI16, IFIT1, MDA5, and RIG-I...
April 1, 2019: Journal of Virology
https://read.qxmd.com/read/30286211/microvesicles-from-malaria-infected-red-blood-cells-activate-natural-killer-cells-via-mda5-pathway
#38
JOURNAL ARTICLE
Weijian Ye, Marvin Chew, Jue Hou, Fritz Lai, Stije J Leopold, Hooi Linn Loo, Aniruddha Ghose, Ashok K Dutta, Qingfeng Chen, Eng Eong Ooi, Nicholas J White, Arjen M Dondorp, Peter Preiser, Jianzhu Chen
Natural killer (NK) cells provide the first line of defense against malaria parasite infection. However, the molecular mechanisms through which NK cells are activated by parasites are largely unknown, so is the molecular basis underlying the variation in NK cell responses to malaria infection in the human population. Here, we compared transcriptional profiles of responding and non-responding NK cells following exposure to Plasmodium-infected red blood cells (iRBCs) and identified MDA5, a RIG-I-like receptor involved in sensing cytosolic RNAs, to be differentially expressed...
October 2018: PLoS Pathogens
https://read.qxmd.com/read/29559532/innate-responses-to-gene-knockouts-impact-overlapping-gene-networks-and-vary-with-respect-to-resistance-to-viral-infection
#39
JOURNAL ARTICLE
Yonghong Liu, Yuanyuan Liu, Jiaming Wu, Bernard Roizman, Grace Guoying Zhou
Analyses of the levels of mRNAs encoding IFIT1, IFI16, RIG-1, MDA5, CXCL10, LGP2, PUM1, LSD1, STING, and IFNβ in cell lines from which the gene encoding LGP2, LSD1, PML, HDAC4, IFI16, PUM1, STING, MDA5, IRF3, or HDAC 1 had been knocked out, as well as the ability of these cell lines to support the replication of HSV-1, revealed the following: ( i ) Cell lines lacking the gene encoding LGP2, PML, or HDAC4 (cluster 1) exhibited increased levels of expression of partially overlapping gene networks. Concurrently, these cell lines produced from 5 fold to 12 fold lower yields of HSV-1 than the parental cells...
April 3, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/29395325/human-adar1-prevents-endogenous-rna-from-triggering-translational-shutdown
#40
JOURNAL ARTICLE
Hachung Chung, Jorg J A Calis, Xianfang Wu, Tony Sun, Yingpu Yu, Stephanie L Sarbanes, Viet Loan Dao Thi, Abigail R Shilvock, H-Heinrich Hoffmann, Brad R Rosenberg, Charles M Rice
Type I interferon (IFN) is produced when host sensors detect foreign nucleic acids, but how sensors differentiate self from nonself nucleic acids, such as double-stranded RNA (dsRNA), is incompletely understood. Mutations in ADAR1, an adenosine-to-inosine editing enzyme of dsRNA, cause Aicardi-Goutières syndrome, an autoinflammatory disorder associated with spontaneous interferon production and neurologic sequelae. We generated ADAR1 knockout human cells to explore ADAR1 substrates and function. ADAR1 primarily edited Alu elements in RNA polymerase II (pol II)-transcribed mRNAs, but not putative pol III-transcribed Alus...
February 8, 2018: Cell
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