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https://www.readbyqxmd.com/read/28634194/zbp1-dai-ubiquitination-and-sensing-of-influenza-vrnps-activate-programmed-cell-death
#1
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/28625874/negative-regulation-of-the-rlh-signaling-by-the-e3-ubiquitin-ligase-rnf114
#2
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/28613140/influenza-virus-protein-pb1-f2-interacts-with-calcoco2-ndp52-to-modulate-innate-immune-response
#3
Olivier Leymarie, Léa Meyer, Lionel Tafforeau, Vincent Lotteau, Bruno Da Costa, Bernard Delmas, Christophe Chevalier, Ronan Le Goffic
PB1-F2 is a viral protein encoded by influenza A viruses (IAVs). PB1-F2 is implicated in virulence by triggering immune cell apoptosis and enhancing inflammation. To obtain an insight into the molecular mechanisms of PB1-F2-mediated virulence, we used the yeast two-hybrid approach to find new PB1-F2 cellular interactors. This allowed us to identify calcium-binding and coiled-coil domain 2 (CALCOCO2, also known as NDP52) as a binding partner of PB1-F2. Binding of PB1-F2 to CALCOCO2 was confirmed by pull-down...
June 14, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28607490/multiple-truncated-isoforms-of-mavs-prevent-its-spontaneous-aggregation-in-antiviral-innate-immune-signalling
#4
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/28594325/cyclophilin-a-regulated-ubiquitination-is-critical-for-rig-i-mediated-antiviral-immune-responses
#5
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/28576493/the-suppression-of-innate-immune-response-by-human-rhinovirus-c
#6
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/28566766/identification-of-a-small-molecule-that-primes-the-type-i-interferon-response-to-cytosolic-dna
#7
Samira Khiar, Marianne Lucas-Hourani, Sébastien Nisole, Nikaïa Smith, Olivier Helynck, Maryline Bourgine, Claude Ruffié, Jean-Philippe Herbeuval, Hélène Munier-Lehmann, Frédéric Tangy, Pierre-Olivier Vidalain
The type I interferon response plays a pivotal role in host defense against infectious agents and tumors, and promising therapeutic approaches rely on small molecules designed to boost this system. To identify such compounds, we developed a high-throughput screening assay based on HEK-293 cells expressing luciferase under the control of Interferon-Stimulated Response Elements (ISRE). An original library of 10,000 synthetic compounds was screened, and we identified a series of 1H-benzimidazole-4-carboxamide compounds inducing the ISRE promoter sequence, specific cellular Interferon-Stimulated Genes (ISGs), and the phosphorylation of Interferon Regulatory Factor (IRF) 3...
May 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28566380/seneca-valley-virus-suppresses-host-type-i-interferon-production-by-targeting-adaptor-proteins-mavs-trif-and-tank-for-cleavage
#8
Suhong Qian, Wenchun Fan, Tingting Liu, Mengge Wu, Huawei Zhang, Xiaofang Cui, Yun Zhou, Junjie Hu, Shaozhong Wei, Huanchun Chen, Xiangmin Li, Ping Qian
Seneca Valley Virus (SVV) is an oncolytic RNA virus belonging to the Picornaviridae family. Its nucleotide sequence is highly similar to those of members of the Cardiovirus genus. SVV is also a neuroendocrine cancer-selective oncolytic picornavirus that can be used for anti-cancer therapy. However, the interaction between SVV and its host is yet to be fully characterized. In this study, SVV inhibited antiviral type I interferon (IFN) responses by targeting different host adaptors, including mitochondrial anti-viral signaling (MAVS), Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF), and TRAF family member-associated NF-κB activator (TANK) via viral 3C(pro) SVV 3C(pro) mediated the cleavage of MAVS, TRIF, and TANK at specific sites, which required its protease activity...
May 31, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28558073/hepatitis-e-virus-persists-in-the-presence-of-a-type-iii-interferon-response
#9
Xin Yin, Xinlei Li, Charuta Ambardekar, Zhimin Hu, Sébastien Lhomme, Zongdi Feng
The RIG-I-like RNA helicase (RLR)-mediated interferon (IFN) response plays a pivotal role in the hepatic antiviral immunity. The hepatitis A virus (HAV) and the hepatitis C virus (HCV) counter this response by encoding a viral protease that cleaves the mitochondria antiviral signaling protein (MAVS), a common signaling adaptor for RLRs. However, a third hepatotropic RNA virus, the hepatitis E virus (HEV), does not appear to encode a functional protease yet persists in infected cells. We investigated HEV-induced IFN responses in human hepatoma cells and primary human hepatocytes...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28549220/physiological-responses-during-intermittent-running-exercise-differ-between-outdoor-and-treadmill-running
#10
Marco Panascì, Romuald Lepers, Antonio La Torre, Matteo Bonato, Hervè Assadi
The aim of this study was to compare the physiological responses during 15 min of intermittent running consisting of 30 s high intensity running exercise at maximal aerobic velocity (MAV) interspersed with 30 s passive recovery (30-30) performed outdoor versus on a motorized treadmill. Fifteen collegiate physically active males (age: 22±1 years-old; body mass: 66±7 kg; stature: 176±06 cm, weekly training volume: 5±2 h·week<sup>-1</sup>), performed Fitness Intermittent test 45-15 in order to determine VO<sub>2max</sub> and Maximal Aerobic Velocity (MAV) and then completed in random order three different training sessions consisting of 30s run -30s rest outdoor on athletic track (30-30 Track) at MAV; 30s run -30s rest on treadmill (30-30 Treadmill) at MAV; 30s run -30s rest at MAV+15% (30-30+15% MAV Treadmill)...
May 26, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28542569/fas-associated-factor-1-positively-regulates-type-i-interferon-response-to-rna-virus-infection-by-targeting-nlrx1
#11
Jae-Hoon Kim, Min-Eun Park, Chamilani Nikapitiya, Tae-Hwan Kim, Md Bashir Uddin, Hyun-Cheol Lee, Eunhee Kim, Jin Yeul Ma, Jae U Jung, Chul-Joong Kim, Jong-Soo Lee
FAS-associated factor-1 (FAF1) is a component of the death-inducing signaling complex involved in Fas-mediated apoptosis. It regulates NF-κB activity, ubiquitination, and proteasomal degradation. Here, we found that FAF1 positively regulates the type I interferon pathway. FAF1gt/gt mice, which deficient in FAF1, and FAF1 knockdown immune cells were highly susceptible to RNA virus infection and showed low levels of inflammatory cytokines and type I interferon (IFN) production. FAF1 was bound competitively to NLRX1 and positively regulated type I IFN signaling by interfering with the interaction between NLRX1 and MAVS, thereby freeing MAVS to bind RIG-I, which switched on the MAVS-RIG-I-mediated antiviral signaling cascade...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28527664/a-new-hdv-mouse-model-identifies-mitochondrial-antiviral-signaling-protein-mavs-as-a-key-player-in-ifn-%C3%AE-induction
#12
Lester Suárez-Amarán, Carla Usai, Marianna Di Scala, Cristina Godoy, Yi Ni, Mirja Hommel, Laura Palomo, Víctor Segura, Cristina Olagüe, Africa Vales, Alicia Ruiz-Ripa, Maria Buti, Eduardo Salido, Jesús Prieto, Stephan Urban, Francisco Rodríguez-Frias, Rafael Aldabe, Gloria González-Aseguinolaza
BACKGROUND & AIMS: Studying hepatitis delta virus (HDV) and developing new treatments is hampered by the limited availability of small animal models. Here a description of a robust mouse model of HDV infection that mimics several important characteristics of the human disease is presented. METHODS: HDV- and HBV-replication competent genomes were delivered to the mouse liver using adeno-associated viruses (AAV) (AAV-HDV and AAV-HBV). Viral load, antigen expression and genomes were quantified at different time points after AAV injection...
May 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28512148/erratum-for-the-research-article-reactive-oxygen-species-induce-virus-independent-mavs-oligomerization-in-systemic-lupus-erythematosus-by-i-a-buskiewicz-t-montgomery-e-c-yasewicz-s-a-huber-m-p-murphy-r-c-hartley-r-kelly-m-k-crow-a-perl-r-c-budd-a-koenig
#13
https://www.readbyqxmd.com/read/28511661/a-preliminary-investigation-on-the-utility-of-temporal-features-of-force-myography-in-the-two-class-problem-of-grasp-vs-no-grasp-in-the-presence-of-upper-extremity-movements
#14
Gautam P Sadarangani, Carlo Menon
BACKGROUND: In upper-extremity stroke rehabilitation applications, the potential use of Force Myography (FMG) for detecting grasping is especially relevant, as the presence of grasping may be indicative of functional activity, which is a key goal of rehabilitation. To date, most FMG research has focused on the classification of the raw FMG signal (i.e. instantaneous FMG samples) in order to determine the state of the hand. However, given the temporal nature of force generation during grasping, the use of temporal feature extraction techniques may yield increased accuracy...
May 16, 2017: Biomedical Engineering Online
https://www.readbyqxmd.com/read/28480979/down-regulation-of-trif-tlr3-and-mavs-in-hcv-infected-liver-correlates-with-the-outcome-of-infection
#15
Premashis Kar, Deepak Kumar, Phani Kumar Gumma, Soumya Jyoti Chowdhury, Vijay Kumar Karra
AIMS: In virus-infected cells, pattern recognition receptors (PRRs) recruits their specific adaptor molecules, mitochondrial antiviral signaling protein (MAVS), TIR-domain-containing adapter-inducing interferon-β (TRIF) and TNF receptor associated factor (TRAF6) which induces interferon. Toll-like receptor 3 (TLR3) induces activation of the NF-kappa B (NF-κB) for interferon production. The study has been designed to assess the correlation of TLR3, MAVS, TRIF and TRAF6 outcome of HCV infection...
May 8, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28473813/asunaprevir-evokes-hepatocytes-innate-immunity-to-restrict-the-replication-of-hepatitis-c-and-dengue-virus
#16
Wei-Lun Tsai, Jin-Shiung Cheng, Chih-Wen Shu, Kwok-Hung Lai, Hoi-Hung Chan, Chun-Ching Wu, Jing-Mei Wu, Ping-I Hsu, Raymond T Chung, Tsung-Hsien Chang
Type I Interferon-mediated innate immunity against Flaviviridae, such as Hepatitis C virus (HCV) and Dengue virus (DENV), involves TLR3, RIG-I-like receptor (RLR) and JAK-STAT signal pathways. Asunaprevir is a newly developed HCV protease inhibitor for HCV treatment. Whether, asunaprevir activates innate immunity to restrict viral infection is unclear. Thus, this study investigates the effect of asunaprevir on innate immunity and its influence on HCV and DENV infection. Huh 7.5.1, Hep-G2 cells, JFH-1 infection model, and DENV-2 infection were used for the analysis...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28471483/human-sle-bone-marrow-mesenchymal-stem-cells-bmscs-have-a-senescence-associated-secretory-phenotype-sasp-mediated-by-a-mavs-ifn%C3%AE-feedback-loop
#17
Lin Gao, Anna K Bird, Nida Meednu, Kristin Dauenhauer, Jane Liesveld, Jennifer Anolik, R John Looney
Objective - BMSCs create a special microenvironment for hematopoiesis and immunity and also display robust immunomodulatory properties which are impaired in SLE. This study was undertaken to define the mechanisms of defects in human SLE BMSCs. Methods - Patients fulfilling SLE classification criteria and healthy controls were recruited under an Institutional Review Board approved protocol (n=6 each). BMSCs were isolated with low density Ficoll/Hypaque. BMSCs were verified by flow cytometry and studied using immunocytochemistry, real-time PCR, western blotting, comet assay, beta-galactosidase assay, and RNA interference...
May 4, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28469175/ube2d3-and-ube2n-are-essential-for-rig-i-mediated-mavs-aggregation-in-antiviral-innate-immunity
#18
Yuheng Shi, Bofeng Yuan, Wenting Zhu, Rui Zhang, Lin Li, Xiaojing Hao, She Chen, Fajian Hou
Innate immunity plays a pivotal role in virus infection. RIG-I senses viral RNA and initiates an effective innate immune response for type I interferon production. To transduce RIG-I-mediated antiviral signalling, a mitochondrial protein MAVS forms prion-like aggregates to activate downstream kinases and transcription factors. However, the activation mechanism of RIG-I is incompletely understood. Here we identify two ubiquitin enzymes Ube2D3 and Ube2N through chromatographic purification as activators for RIG-I on virus infection...
May 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28466692/dna-methylation-changes-in-tbx3-in-a-mouse-model-exposed-to-polybrominated-diphenyl-ethers
#19
Takashi Shimbo, June K Dunnick, Amy Brix, Deepak Mav, Ruchir Shah, John D Roberts, Paul A Wade
DE-71, a commercial mixture of polybrominated diphenyl ethers widely used in flame retardants, is a pervasive environmental contaminant due to its continuing release from waste material and its long half-life in humans. Although the genotoxic potential of DE-71 appears to be low based on bacterial mutagenicity, it remains a public health concern due to its reported involvement in tumor development. Molecular mechanisms by which DE-71 influences tumor incidence or progression remain understudied. We used liver carcinoma tissue from mice exposed to DE-71 to test the hypothesis that epigenetic alterations consistent with tumor development, specifically DNA methylation, result from long-term DE-71 exposure...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28465426/a-novel-agonist-of-the-trif-pathway-induces-a-cellular-state-refractory-to-replication-of-zika-chikungunya-and-dengue-viruses
#20
Kara M Pryke, Jinu Abraham, Tina M Sali, Bryan J Gall, Iris Archer, Andrew Liu, Shelly Bambina, Jason Baird, Michael Gough, Marita Chakhtoura, Elias K Haddad, Ilsa T Kirby, Aaron Nilsen, Daniel N Streblow, Alec J Hirsch, Jessica L Smith, Victor R DeFilippis
The ongoing concurrent outbreaks of Zika, Chikungunya, and dengue viruses in Latin America and the Caribbean highlight the need for development of broad-spectrum antiviral treatments. The type I interferon (IFN) system has evolved in vertebrates to generate tissue responses that actively block replication of multiple known and potentially zoonotic viruses. As such, its control and activation through pharmacological agents may represent a novel therapeutic strategy for simultaneously impairing growth of multiple virus types and rendering host populations resistant to virus spread...
May 2, 2017: MBio
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