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https://www.readbyqxmd.com/read/28636653/the-ebola-virus-vp35-protein-binds-viral-immunostimulatory-and-host-rnas-identified-through-deep-sequencing
#1
Kari A Dilley, Alexander A Voorhies, Priya Luthra, Vinita Puri, Timothy B Stockwell, Hernan Lorenzi, Christopher F Basler, Reed S Shabman
Ebola virus and Marburg virus are members of the Filovirdae family and causative agents of hemorrhagic fever with high fatality rates in humans. Filovirus virulence is partially attributed to the VP35 protein, a well-characterized inhibitor of the RIG-I-like receptor pathway that triggers the antiviral interferon (IFN) response. Prior work demonstrates the ability of VP35 to block potent RIG-I activators, such as Sendai virus (SeV), and this IFN-antagonist activity is directly correlated with its ability to bind RNA...
2017: PloS One
https://www.readbyqxmd.com/read/28634194/zbp1-dai-ubiquitination-and-sensing-of-influenza-vrnps-activate-programmed-cell-death
#2
Sannula Kesavardhana, Teneema Kuriakose, Clifford S Guy, Parimal Samir, R K Subbarao Malireddi, Ashutosh Mishra, Thirumala-Devi Kanneganti
Innate sensing of influenza virus infection induces activation of programmed cell death pathways. We have recently identified Z-DNA-binding protein 1 (ZBP1) as an innate sensor of influenza A virus (IAV). ZBP1-mediated IAV sensing is critical for triggering programmed cell death in the infected lungs. Surprisingly, little is known about the mechanisms regulating ZBP1 activation to induce programmed cell death. Here, we report that the sensing of IAV RNA by retinoic acid inducible gene I (RIG-I) initiates ZBP1-mediated cell death via the RIG-I-MAVS-IFN-β signaling axis...
June 20, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28631605/loss-of-sendai-virus-c-protein-leads-to-accumulation-of-rig-i-immunostimulatory-defective-interfering-rna
#3
Maria Teresa Sánchez-Aparicio, Dominique Garcin, Charles M Rice, Daniel Kolakofsky, Adolfo García-Sastre, Alina Baum
Retinoic acid inducible gene (RIG-I)-mediated innate immunity plays a pivotal role in defence against virus infections. Previously we have shown that Sendai virus (SeV) defective interfering (DI) RNA functions as an exclusive and potent RIG-I ligand in DI-RNA-rich SeV-Cantell infected cells. To further understand how RIG-I is activated during SeV infection, we used a different interferon (IFN)-inducing SeV strain, recombinant SeVΔC, which, in contrast to SeV-Cantell is believed to stimulate IFN production due to the lack of the SeV IFN antagonist protein C...
June 20, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28625874/negative-regulation-of-the-rlh-signaling-by-the-e3-ubiquitin-ligase-rnf114
#4
Boren Lin, Qi Ke, Haiying Li, Nichole S Pheifer, David C Velliquette, Douglas W Leaman
The retinoic acid-inducible gene-I (RIG-I)-like helicases (RLH)s are cytoplasmic pattern recognition receptors expressed in both immune and non-immune cells that are essential for detection of intracellular RNA products, primarily of viral origin. Upon binding to viral RNA, RLHs interact with mitochondrial antiviral signaling protein (MAVS) to activate interferon (IFN)-mediated antiviral responses. The RLH/MAVS signaling pathway is regulated by ubiquitination/deubiquitination, in which several ubiquitin-editing proteins play critical roles...
June 15, 2017: Cytokine
https://www.readbyqxmd.com/read/28625551/sensing-self-and-foreign-circular-rnas-by-intron-identity
#5
Y Grace Chen, Myoungjoo V Kim, Xingqi Chen, Pedro J Batista, Saeko Aoyama, Jeremy E Wilusz, Akiko Iwasaki, Howard Y Chang
Circular RNAs (circRNAs) are single-stranded RNAs that are joined head to tail with largely unknown functions. Here we show that transfection of purified in vitro generated circRNA into mammalian cells led to potent induction of innate immunity genes and confers protection against viral infection. The nucleic acid sensor RIG-I is necessary to sense foreign circRNA, and RIG-I and foreign circRNA co-aggregate in cytoplasmic foci. CircRNA activation of innate immunity is independent of a 5' triphosphate, double-stranded RNA structure, or the primary sequence of the foreign circRNA...
June 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28615462/posttranslational-modification-as-a-critical-determinant-of-cytoplasmic-innate-immune-recognition
#6
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/28609250/recognition-of-viral-rna-by-pattern-recognition-receptors-in-the-induction-of-innate-immunity-and-excessive-inflammation-during-respiratory-viral-infections
#7
Masaaki Okamoto, Hirotake Tsukamoto, Takahisa Kouwaki, Tsukasa Seya, Hiroyuki Oshiumi
The innate immune system is the first line of defense against virus infection that triggers the expression of type I interferon (IFN) and proinflammatory cytokines. Pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns, resulting in the induction of innate immune responses. Viral RNA in endosomes is recognized by Toll-like receptors, and cytoplasmic viral RNA is recognized by RIG-I-like receptors. The host innate immune response is critical for protection against virus infection...
June 13, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28607490/multiple-truncated-isoforms-of-mavs-prevent-its-spontaneous-aggregation-in-antiviral-innate-immune-signalling
#8
Nan Qi, Yuheng Shi, Rui Zhang, Wenting Zhu, Bofeng Yuan, Xiaoyan Li, Changwan Wang, Xuewu Zhang, Fajian Hou
In response to virus infection, RIG-I-like receptors (RLRs) sense virus RNA and induce MAVS to form prion-like aggregates to further propagate antiviral signalling. Although monomeric MAVS recombinant protein can assemble into prion-like filaments spontaneously in vitro, endogenous MAVS in cells is prevented from aggregation until viral infection. The mechanism preventing cellular MAVS from spontaneous aggregation is unclear. Here we show that multiple N-terminal truncated isoforms of MAVS are essential in preventing full-length MAVS from spontaneous aggregation through transmembrane domain-mediated homotypic interaction...
June 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28595092/ebolavirus-protein-vp24-interferes-with-innate-immune-responses-by-inhibiting-interferon-%C3%AE-1-gene-expression
#9
Felix He, Krister Melén, Sari Maljanen, Rickard Lundberg, Miao Jiang, Pamela Österlund, Laura Kakkola, Ilkka Julkunen
Ebolaviruses (EBOV) cause severe disease with a recent outbreak in West Africa in 2014-2015 leading to more than 28 000 cases and 11 300 fatalities. This emphasizes the urgent need for better knowledge on these highly pathogenic RNA viruses. Host innate immune responses play a key role in restricting the spread of a viral disease. In this study we systematically analyzed the effects of cloned EBOV genes on the main host immune response to RNA viruses: the activation of RIG-I pathway and type I and III interferon (IFN) gene expression...
June 5, 2017: Virology
https://www.readbyqxmd.com/read/28594325/cyclophilin-a-regulated-ubiquitination-is-critical-for-rig-i-mediated-antiviral-immune-responses
#10
Wei Liu, Jing Li, Weinan Zheng, Yingli Shang, Zhendong Zhao, Shanshan Wang, Yuhai Bi, Shuang Zhang, Chongfeng Xu, Ziyuan Duan, Lianfeng Zhang, Yue Lynn Wang, Zhengfan Jiang, Wenjun Liu, Lei Sun
RIG-I is a key cytosolic pattern recognition receptor that interacts with MAVS to induce type I interferons (IFNs) against RNA virus infection. In this study, we found that cyclophilin A (CypA), a peptidyl-prolyl cis/trans isomerase, functioned as a critical positive regulator of RIG-I-mediated antiviral immune responses. Deficiency of CypA impaired RIG-I-mediated type I IFN production and promoted viral replication in human cells and mice. Upon Sendai virus infection, CypA increased the interaction between RIG-I and its E3 ubiquitin ligase TRIM25, leading to enhanced TRIM25-mediated K63-linked ubiquitination of RIG-I that facilitated recruitment of RIG-I to MAVS...
June 8, 2017: ELife
https://www.readbyqxmd.com/read/28593618/rig-i-a-multifunctional-protein-beyond-a-pattern-recognition-receptor
#11
REVIEW
Xiao-Xiao Xu, Han Wan, Li Nie, Tong Shao, Li-Xin Xiang, Jian-Zhong Shao
It was widely known that retinoic acid inducible gene I (RIG-I) functions as a cytosolic pattern recognition receptor that initiates innate antiviral immunity by detecting exogenous viral RNAs. However, recent studies showed that RIG-I participates in other various cellular activities by sensing endogenous RNAs under different circumstances. For example, RIG-I facilitates the therapy resistance and expansion of breast cancer cells and promotes T cell-independent B cell activation through interferon signaling activation by recognizing non-coding RNAs and endogenous retroviruses in certain situations...
June 8, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28592535/newcastle-disease-virus-establishes-persistent-infection-in-tumor-cells-in-vitro-contribution-of-the-cleavage-site-of-fusion-protein-and-second-sialic-acid-binding-site-of-hemagglutinin-neuraminidase
#12
Udaya S Rangaswamy, Weijia Wang, Xing Cheng, Patrick McTamney, Danielle Carroll, Hong Jin
Newcastle Disease Virus (NDV) is an oncolytic virus being developed for the treatment of cancer. Following infection of an ovarian human cancer cell line (OVCAR3) with a recombinant low pathogenic NDV, persistent infection (PI) was established in a subset of tumor cells. PI cells exhibited resistance to superinfection with NDV, and an anti-viral state as demonstrated by upregulation of interferon and interferon induced genes such as Myxoma resistance gene 1 (Mx1) and Retinoic acid-inducing gene-I (RIG-I). Viruses released from PI cells induced higher cell to cell fusion following infection compared to the parental virus in two tumor cell lines tested, HT1080 and HeLa, and remained to be attenuated in chickens...
June 7, 2017: Journal of Virology
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
#13
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/28588282/comparison-and-immunobiological-characterization-of-retinoic-acid-inducible-gene-i-like-receptor-expression-in-mesenchymal-stromal-cells
#14
Gordana Raicevic, Mehdi Najar, Hélène Busser, Emerence Crompot, Dominique Bron, Michel Toungouz, Laurence Lagneaux
Due to their immunomodulatory and regenerative properties, Mesenchymal stromal cells (MSC) have generated major interests in several clinical settings including transplantation and inflammatory diseases. MSC functions can be influenced by their tissue origin. Their microenvironment strongly affects their biology notably through TLR sensing. In this study, we show that MSC isolated from four different sources express another type of cytosolic pathogen recognition receptors known as retinoic acid inducible gene-I (RIG-I)-like receptors (RLR)...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28580319/the-association-of-oasl-and-type-i-interferons-in-the-pathogenesis-and-survival-of-intracellular-replicating-bacterial-species
#15
REVIEW
Gina Leisching, Ian Wiid, Bienyameen Baker
The type I IFN response quickly became associated with its role in the innate immune response to viral infection. The past few years have seen the significance of IFNs expand in breadth to include non-viral pathogens. Previous work has identified that following viral infection, type I IFN signaling induces the production of the 2'-5'-oligoadenylate synthetase (OAS) family, which include OAS1, OAS2, OAS3, and OAS-like (OASL) protein. OASL was identified to be strongly induced following viral infection through engaging the RNA sensor RIG-I and increasing signaling through this pathway to enhance the anti-viral type I IFN response...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28576493/the-suppression-of-innate-immune-response-by-human-rhinovirus-c
#16
Li-Li Pang, Xin-Hui Yuan, Chang-Sheng Shao, Mao-Zhong Li, Ying Wang, Hui-Min Wang, Guang-Cheng Xie, Zhi-Ping Xie, Yue Yuan, Dong-Mei Zhou, Xiao-Man Sun, Qing Zhang, Yan Xin, Dan-di Li, Zhao-Jun Duan
Rhinovirus C (RV-C), a newly identified group of human rhinoviruses (RVs), is associated with exacerbation of severe asthma. The type I interferon (IFN) response induced by this virus and the mechanisms of evasion of IFN-mediated innate immunity for RV-C remain unclear. In this study, we constructed a full-length cDNA clone of RV-C (LZ651) from a clinical sample. IFN-β mRNA and protein levels were not elevated in differentiated Human bronchial epithelial (HBE) cells at the air-liquid interface infected with RV-C, except in the early stage of infection...
May 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28574756/sod2-facilitates-the-antiviral-innate-immune-response-by-scavenging-reactive-oxygen-species
#17
Wan Wang, Yufei Jin, Ningxiang Zeng, Qingwei Ruan, Feng Qian
Superoxide dismutase 2 (SOD2) is essential in radical scavenging, which balances the intracellular level of reactive oxygen species (ROS). The dysfunction of SOD2 is associated with increasing incidence of various human diseases, including cancer, neuron diseases, and myocardial defects. However, the connections between SOD2-mediated oxidative homeostasis and innate immune response remain unclear. In this study, we report that SOD2 is a crucial regulator of antiviral signaling. Depletion of SOD2 impairs RNA virus-induced type I interferon (IFN) and proinflammatory cytokine production, resulting in enhanced viral replication...
June 2, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28573616/assays-to-measure-suppression-of-type-i-interferon-responses-by-filovirus-vp35-proteins
#18
Priya Luthra, Christopher F Basler
Innate immunity is the first line of defense against virus infections and is marked by production of type I interferons (IFN), a family of cytokines that includes IFN-β and several IFN-αs. For the filoviruses and many other RNA viruses that replicate in the cytoplasm, the RIG-I-like pattern recognition receptors (RLRs) are potential triggers of IFN production. To counteract such innate antiviral responses, many viruses encode proteins that antagonize RLR signaling. Ebola virus (EBOV) and other filoviruses produce VP35 proteins that block IFN induction via RLR signaling...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28560754/oncostatin-m-induces-rig-i-and-mda5-expression-and-enhances-the-double-stranded-rna-response-in-fibroblasts
#19
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/28559402/findings-may-lead-to-new-strategies-for-gvhd
#20
(no author information available yet)
A new study in mice demonstrates that activating the RIG-I and STING signaling pathways, normally associated with antiviral immunity, can help protect the intestinal epithelium from damage caused by chemotherapy and radiation following stem cell transplantation. The findings may help in developing strategies to prevent graft-versus-host disease in patients with leukemia and other blood disorders.
May 30, 2017: Cancer Discovery
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