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https://www.readbyqxmd.com/read/29688572/enhanced-expression-of-ifi16-and-rig-i-in-human-third-trimester-placentas-following-hsv-1-infection
#1
Agnieszka Jabłońska, Mirosława Studzińska, Patrycja Suski, Jarosław Kalinka, Edyta Paradowska
The innate immune response in the placenta depends on the ability of maternal immune cells and fetal trophoblast cells to detect and eliminate invading pathogens through germline-encoded pattern recognition receptors (PRRs). In the present study, we analyzed the transcripts and protein expression of IFI16, MDA5, RIG-I, and TLR3 in third-trimester human placentas and investigated cytokine profiles generated during herpes simplex type 1 (HSV-1) infection. Decidual and chorionic villous biopsies (38-42 week of gestation) were obtained from healthy women immediately after a cesarean section...
April 24, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29686974/sirt6-acts-as-a-negative-regulator-in-dengue-virus-induced-inflammatory-response-by-targeting-the-dna-binding-domain-of-nf-%C3%AE%C2%BAb-p65
#2
Pengcheng Li, Yufei Jin, Fei Qi, Fangyi Wu, Susu Luo, Yuanjiu Cheng, Ruth R Montgomery, Feng Qian
Dengue virus (DENV) is a mosquito-borne single-stranded RNA virus causing human disease with variable severity. The production of massive inflammatory cytokines in dengue patients has been associated with dengue disease severity. However, the regulation of these inflammatory responses remains unclear. In this study, we report that SIRT6 is a negative regulator of innate immune responses during DENV infection. Silencing of Sirt6 enhances DENV-induced proinflammatory cytokine and chemokine production. Overexpression of SIRT6 inhibits RIG-I-like receptor (RLR) and Toll-like receptor 3 (TLR3) mediated NF-κB activation...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29686682/targeting-cytosolic-nucleic-acid-sensing-pathways-for-cancer-immunotherapies
#3
REVIEW
Sandra Iurescia, Daniela Fioretti, Monica Rinaldi
The innate immune system provides the first line of defense against pathogen infection though also influences pathways involved in cancer immunosurveillance. The innate immune system relies on a limited set of germ line-encoded sensors termed pattern recognition receptors (PRRs), signaling proteins and immune response factors. Cytosolic receptors mediate recognition of danger damage-associated molecular patterns (DAMPs) signals. Once activated, these sensors trigger multiple signaling cascades, converging on the production of type I interferons and proinflammatory cytokines...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29686409/vibrio-vulnificus-quorum-sensing-molecule-cyclo-phe-pro-inhibits-rig-i-mediated-antiviral-innate-immunity
#4
Wooseong Lee, Seung-Hoon Lee, Minwoo Kim, Jae-Su Moon, Geon-Woo Kim, Hae-Gwang Jung, In Hwang Kim, Ji Eun Oh, Hi Eun Jung, Heung Kyu Lee, Keun Bon Ku, Dae-Gyun Ahn, Seong-Jun Kim, Kun-Soo Kim, Jong-Won Oh
The recognition of pathogen-derived ligands by pattern recognition receptors activates the innate immune response, but the potential interaction of quorum-sensing (QS) signaling molecules with host anti-viral defenses remains largely unknown. Here we show that the Vibrio vulnificus QS molecule cyclo(Phe-Pro) (cFP) inhibits interferon (IFN)-β production by interfering with retinoic-acid-inducible gene-I (RIG-I) activation. Binding of cFP to the RIG-I 2CARD domain induces a conformational change in RIG-I, preventing the TRIM25-mediated ubiquitination to abrogate IFN production...
April 23, 2018: Nature Communications
https://www.readbyqxmd.com/read/29681974/baicalin-downregulates-rlrs-signaling-pathway-to-control-influenza-a-virus-infection-and-improve-the-prognosis
#5
Peng Pang, Ke Zheng, Sizhi Wu, Huachong Xu, Li Deng, Yucong Shi, Xiaoyin Chen
The objective of this study is to investigate the effects of baicalin on controlling the pulmonary infection and improving the prognosis in influenza A virus (IAV) infection. PCR and western blot were used to measure the changes of some key factors in RLRs signaling pathway. MSD electrochemiluminescence was used to measure the expression of pulmonary inflammatory cytokines including IFN- γ , TNF- α , IL-1 β , IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, and KC/GRO. Flow cytometry was used to detect the proportion of Th1, Th2, Th17, and Treg...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29678949/hu-antigen-r-regulates-antiviral-innate-immune-responses-through-the-stabilization-of-mrna-for-polo-like-kinase-2
#6
Takuya Sueyoshi, Takumi Kawasaki, Yuichi Kitai, Daisuke Ori, Shizuo Akira, Taro Kawai
Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), RIG-I, and melanoma differentiation-associated gene 5 (MDA5) play a critical role in inducing antiviral innate immune responses by activating IFN regulatory factor 3 (IRF3) and NF-κB, which regulates the transcription of type I IFN and inflammatory cytokines. Antiviral innate immune responses are also regulated by posttranscriptional and translational mechanisms. In this study, we identified an RNA-binding protein HuR as a regulator for RLR signaling...
April 20, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29677479/rig-i-and-other-rna-sensors-in-antiviral-immunity
#7
Kwan T Chow, Michael Gale, Yueh-Ming Loo
Pattern recognition receptors (PRRs) survey intra- and extracellular spaces for pathogen-associated molecular patterns (PAMPs) within microbial products of infection. Recognition and binding to cognate PAMP ligand by specific PRRs initiates signaling cascades that culminate in a coordinated intracellular innate immune response designed to control infection. In particular, our immune system has evolved specialized PRRs to discriminate viral nucleic acid from host. These are critical sensors of viral RNA to trigger innate immunity in the vertebrate host...
April 26, 2018: Annual Review of Immunology
https://www.readbyqxmd.com/read/29677136/cytoplasmic-translocation-of-nucleolar-protein-nop53-promotes-viral-replication-by-suppressing-host-defense
#8
Wen Meng, Shi-Chong Han, Cui-Cui Li, Hui-Jun Dong, Jian-Yu Chang, Hwa-Chain Robert Wang, Xiao-Jia Wang
NOP53 is a tumor suppressor protein located in the nucleolus and is translocated to the cytoplasm during infection by vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1), as shown in our previous study. Cytoplasmic NOP53 interacts with the retinoic acid-inducible gene I (RIG-I) to remove its K63-linked ubiquitination, leading to attenuation of type I interferon IFN-β. In the present study, we found no obvious translocation of NOP53 in infection by a mutant virus lacking ICP4 (HSV-1/d120, replication inadequate)...
April 20, 2018: Viruses
https://www.readbyqxmd.com/read/29672716/mir-122-does-not-impact-recognition-of-the-hcv-genome-by-innate-sensors-of-rna-but-rather-protects-the-5-end-from-the-cellular-pyrophosphatases-dom3z-and-dusp11
#9
Yalena Amador-Cañizares, Annie Bernier, Joyce A Wilson, Selena M Sagan
Hepatitis C virus (HCV) recruits two molecules of the liver-specific microRNA-122 (miR-122) to the 5' end of its genome. This interaction promotes viral RNA accumulation, but the precise mechanism(s) remain incompletely understood. Previous studies suggest that miR-122 is able to protect the HCV genome from 5' exonucleases (Xrn1/2), but this protection is not sufficient to account for the effect of miR-122 on HCV RNA accumulation. Thus, we investigated whether miR-122 was also able to protect the viral genome from innate sensors of RNA or cellular pyrophosphatases...
April 17, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29669840/arenaviral-nucleoproteins-suppress-pact-induced-augmentation-of-rig-i-function-to-inhibit-type-i-interferon-production
#10
Junjie Shao, Qinfeng Huang, Xiaoying Liu, Da Di, Yuying Liang, Hinh Ly
RIG-I is a major cytoplasmic sensor of viral pathogen-associated molecular pattern (PAMP) RNA and induces the production of type I interferon (IFN) upon viral infection. A dsRNA-binding protein PACT plays an important role in potentiating RIG-I function. We have previously shown that arenaviral nucleoproteins (NPs) suppress type I IFN production via its exoribonuclease (RNase) activity to degrade PAMP RNA. We report here that NPs of arenaviruses block PACT-induced enhancement of RIG-I function to mediate type I IFN production and that the inhibition is dependent on the NP's RNase function, which is different than a known mechanism of other viral proteins to disrupt PACT and RIG-I interaction...
April 18, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29661858/rna-sensor-lgp2-inhibits-traf-ubiquitin-ligase-to-negatively-regulate-innate-immune-signaling
#11
Jean-Patrick Parisien, Jessica J Lenoir, Roli Mandhana, Kenny R Rodriguez, Kenin Qian, Annie M Bruns, Curt M Horvath
The production of type I interferon (IFN) is essential for cellular barrier functions and innate and adaptive antiviral immunity. In response to virus infections, RNA receptors RIG-I and MDA5 stimulate a mitochondria-localized signaling apparatus that uses TRAF family ubiquitin ligase proteins to activate master transcription regulators IRF3 and NFκB, driving IFN and antiviral target gene expression. Data indicate that a third RNA receptor, LGP2, acts as a negative regulator of antiviral signaling by interfering with TRAF family proteins...
April 16, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29649448/retraction-notice-to-the-unfolded-protein-response-element-ire1%C3%AE-senses-bacterial-proteins-invading-the-er-to-activate-rig-i-and-innate-immune-signaling
#12
Jin A Cho, Ann-Hwee Lee, Barbara Platzer, Benedict C S Cross, Brooke M Gardner, Heidi De Luca, Phi Luong, Heather P Harding, Laurie H Glimcher, Peter Walter, Edda Fiebiger, David Ron, Jonathan C Kagan, Wayne I Lencer
No abstract text is available yet for this article.
April 11, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29626090/a-gtpase-activating-protein-binding-protein-g3bp1-antiviral-protein-relay-conveys-arteriosclerotic-wnt-signals-in-aortic-smooth-muscle-cells
#13
Bindu Ramachandran, John N Stabley, Su-Li Cheng, Abraham S Behrmann, Austin Gay, Li Li, Megan Mead, Julia Kozlitina, Andrew Lemoff, Hamid Mirzaei, Zhijian Chen, Dwight A Towler
In aortic vascular smooth muscle (VSM), the canonical Wnt receptor LRP6 inhibits protein arginine (Arg) methylation, a new component of noncanonical Wnt signaling that stimulates nuclear factor of activated T cells (viz., NFATc4). To better understand how methylation mediates these actions, mass spectrometry was performed on VSM cell extracts from control and LRP6-deficient mice. LRP6-dependent Arg methylation was regulated on > 500 proteins; only 21 exhibited increased monomethylation (MMA) with concomitant reductions in dimethylation...
April 6, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29618647/identification-of-the-rna-pseudoknot-within-the-3-end-of-prrsv-genome-as-pathogen-associated-molecular-pattern-to-activate-antiviral-signaling-via-rig-i-and-tlr3
#14
Sha Xie, Xin-Xin Chen, Songlin Qiao, Rui Li, Yangang Sun, Shuangfei Xia, Lin-Jian Wang, Xuegang Luo, Ruiguang Deng, En-Min Zhou, Gai-Ping Zhang
Once infected by viruses, cells can detect pathogen associated molecular patterns (PAMPs) on viral nucleic acid by host pattern recognition receptors (PRRs) to initiate the antiviral response. Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of porcine reproductive and respiratory syndrome (PRRS), characterized by reproductive failure in sows and respiratory diseases in pigs of different ages. To date, the sensing mechanism of PRRSV has not been elucidated. Here, we reported that the pseudoknot region residing in the 3' untranslated regions (UTR) of PRRSV genome, which has been proposed to regulate RNA synthesis and virus replication, was sensed as non-self by retinoic acid-inducible gene I (RIG-I) and Toll like receptor (TLR3) and strongly induced type I IFNs and interferon-stimulated genes (ISGs) in porcine alveolar macrophages (PAMs)...
April 4, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29604449/the-mechanisms-of-ag85a-dna-vaccine-activates-rna-sensors-through-new-signal-transduction
#15
Jingbo Zhai, Qiubo Wang, Yunfeng Gao, Ran Zhang, Shengjun Li, Bing Wei, Yong You, Xun Sun, Changlong Lu
Low immunogenicity is one of the major problems limiting the clinical use for DNA vaccines, which makes it impossible to obtain a strong protective immune response after vaccination. In order to explore whether Ag85A DNA vaccine could mount more efficiently protective immune response through new RNA sensor and its signal transduction pathway of antigen presentation we designed and synthesized Ag85A gene fragment containing multiple points mutations and transfected the gene fragment into the dendritic cell line (DC2...
March 28, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29600494/duox2-induced-innate-immune-responses-in-the-respiratory-epithelium-and-intranasal-delivery-of-duox2-dna-using-polymer-that-mediates-immunization
#16
REVIEW
Yung Jin Jeon, Hyun Jik Kim
Respiratory mucosa especially nasal epithelium is well known as the first-line barrier of air-borne pathogens. High levels of reactive oxygen species (ROS) are detected in in vitro cultured human epithelial cells and in vivo lung. With identification of NADPH oxidase (Nox) system of respiratory epithelium, the antimicrobial role of ROS has been studied. Duox2 is the most abundant Nox isoform and produces the regulated amount of ROS in respiratory epithelium. Duox2-derived ROS are involved in antiviral innate immune responses but more studies are needed to verify the mechanism...
March 30, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29599773/negative-regulation-of-interferon-%C3%AE-production-by-alternative-splicing-of-tumor-necrosis-factor-receptor-associated-factor-3-in-ducks
#17
Xiaoqin Wei, Wei Qian, Suolang Sizhu, Yongtao Li, Kelei Guo, Meilin Jin, Hongbo Zhou
Tumor necrosis factor receptor-associated factor 3 (TRAF3), an intracellular signal transducer, is identified as an important component of Toll-like receptors and RIG-I-like receptors induced type I interferon (IFN) signaling pathways. Previous studies have clarified TRAF3 function in mammals, but little is known about the role of TRAF3 in ducks. Here, we cloned and characterized the full-length duck TRAF3 (duTRAF3) gene and an alternatively spliced isoform of duTRAF3 (duTRAF3-S) lacking the fragment encoding amino acids 217-319, from duck embryo fibroblasts (DEFs)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29593341/mll5-suppresses-antiviral-innate-immune-response-by-facilitating-stub1-mediated-rig-i-degradation
#18
Peipei Zhou, Xiaodan Ding, Xiaoling Wan, Lulu Liu, Xiujie Yuan, Wei Zhang, Xinhui Hui, Guangxun Meng, Hui Xiao, Bin Li, Jin Zhong, Fajian Hou, Lihwen Deng, Yan Zhang
Trithorax group protein MLL5 is an important epigenetic modifier that controls cell cycle progression, chromatin architecture maintenance, and hematopoiesis. However, whether MLL5 has a role in innate antiviral immunity is largely unknown. Here we show that MLL5 suppresses the RIG-I-mediated anti-viral immune response. Mll5-deficient mice infected with vesicular stomatitis virus show enhanced anti-viral innate immunity, reduced morbidity, and viral load. Mechanistically, a fraction of MLL5 located in the cytoplasm interacts with both RIG-I and its E3 ubiquitin ligase STUB1, which promotes K48-linked polyubiquitination and proteasomal degradation of RIG-I...
March 28, 2018: Nature Communications
https://www.readbyqxmd.com/read/29593031/central-role-of-the-nf%C3%AE%C2%BAb-pathway-in-the-scgb1a1-expressing-epithelium-in-mediating-respiratory-syncytial-virus-induced-airway-inflammation
#19
Bing Tian, Jun Yang, Yingxin Zhao, Teodora Ivanciuc, Hong Sun, Maki Wakamiya, Roberto P Garofalo, Allan R Brasier
Lower respiratory tract infection with respiratory syncytial virus (RSV) produces profound inflammation. Despite an understanding of the role of adaptive immunity in RSV infection, the identity of the major sentinel cells initially triggering inflammation is controversial. Here we evaluate the role of nonciliated secretoglobin ( Scgb1a1 )-expressing bronchiolar epithelial cells in RSV infection. Knock-in mice expressing a tamoxifen (TMX)-inducible Cre recombinase (CreERTM ) from the Scgb1a1 locus were crossed with mice that harbor a RelA conditional allele ( RelAfl ), with loxP sites flanking exons 5-8 of the Rel homology domain...
March 28, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29590171/parp1-depletion-induces-rig-i-dependent-signaling-in-human-cancer-cells
#20
Rajib Ghosh, Sanchita Roy, Sonia Franco
DNA Damage Response (DDR) and DNA repair pathways are emerging as potent, ubiquitous suppressors of innate immune signaling in human cells. Here, we show that human cells surviving depletion of the Single Strand Break (SSB) repair protein PARP1 undergo p21-dependent senescence or cell cycle checkpoint activation in the context of activation of innate immune signaling, or viral mimicry. Specifically, we observe induction of a large number of interferon-stimulated genes (ISGs) and multiple pattern recognition receptors (PRRs; including RIG-I, MDA-5, MAVS, TLR3 and STING) and increased nuclear IRF3 staining...
2018: PloS One
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