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https://www.readbyqxmd.com/read/28448848/transmissible-gastroenteritis-virus-infection-induces-nf-%C3%AE%C2%BAb-activation-through-rlr-mediated-signaling
#1
Zhen Ding, Kang An, Lilan Xie, Wei Wu, Ruoxi Zhang, Dang Wang, Ying Fang, Huanchun Chen, Shaobo Xiao, Liurong Fang
Transmissible gastroenteritis virus (TGEV) is a porcine enteric coronavirus which causes lethal severe watery diarrhea in piglets. The pathogenesis of TGEV is strongly associated with inflammation. In this study, we found that TGEV infection activates transcription factors NF-κB, IRF3 and AP-1 in a time- and dose-dependent manner in porcine kidney cells. Treatment with the NF-κB-specific inhibitor BAY11-7082 significantly decreased TGEV-induced proinflammatory cytokine production, but did not affect virus replication...
April 24, 2017: Virology
https://www.readbyqxmd.com/read/28446676/grass-carp-reovirus-vp41-targets-fish-mita-to-abrogate-the-ifn-response
#2
Long-Feng Lu, Shun Li, Zhao-Xi Wang, Si-Qi Du, Dan-Dan Chen, Pin Nie, Yong-An Zhang
Although fish possess an efficient interferon (IFN) system to defend against aquatic virus infection, the grass carp reovirus (GCRV) still causes hemorrhagic disease in grass carp. To date, GCRV's strategy for evading the fish IFN response is still unknown. Here, we report that the GCRV VP41 inhibits fish IFN production by suppressing the phosphorylation of the mediator of IRF3 activation (MITA). First, the activation of the IFN promoter (IFNpro) stimulated by the mitochondrial antiviral signaling protein (MAVS) and MITA was decreased by the overexpression of VP41, whereas such activation induced by TANK-binding kinase 1 (TBK1) was not affected...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28436963/a-sting-activating-nanovaccine-for-cancer-immunotherapy
#3
Min Luo, Hua Wang, Zhaohui Wang, Haocheng Cai, Zhigang Lu, Yang Li, Mingjian Du, Gang Huang, Chensu Wang, Xiang Chen, Matthew R Porembka, Jayanthi Lea, Arthur E Frankel, Yang-Xin Fu, Zhijian J Chen, Jinming Gao
The generation of tumour-specific T cells is critically important for cancer immunotherapy. A major challenge in achieving a robust T-cell response is the spatiotemporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we report a minimalist nanovaccine, comprising a simple physical mixture of an antigen and a synthetic polymeric nanoparticle, PC7A NP, which generates a strong cytotoxic T-cell response with low systemic cytokine expression. Mechanistically, the PC7A NP achieves efficient cytosolic delivery of tumour antigens to antigen-presenting cells in draining lymph nodes, leading to increased surface presentation while simultaneously activating type I interferon-stimulated genes...
April 24, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28436945/adar1-controls-apoptosis-of-stressed-cells-by-inhibiting-staufen1-mediated-mrna-decay
#4
Masayuki Sakurai, Yusuke Shiromoto, Hiromitsu Ota, Chunzi Song, Andrew V Kossenkov, Jayamanna Wickramasinghe, Louise C Showe, Emmanuel Skordalakes, Hsin-Yao Tang, David W Speicher, Kazuko Nishikura
Both p150 and p110 isoforms of ADAR1 convert adenosine to inosine in double-stranded RNA (dsRNA). ADAR1p150 suppresses the dsRNA-sensing mechanism that activates MDA5-MAVS-IFN signaling in the cytoplasm. In contrast, the biological function of the ADAR1p110 isoform, which is usually located in the nucleus, is largely unknown. Here, we show that stress-activated phosphorylation of ADAR1p110 by MKK6-p38-MSK MAP kinases promotes its binding to Exportin-5 and its export from the nucleus. After translocating to the cytoplasm, ADAR1p110 suppresses apoptosis in stressed cells by protecting many antiapoptotic gene transcripts that contain 3'-untranslated-region dsRNA structures primarily comprising inverted Alu repeats...
April 24, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28432927/type-2-bvdv-n-pro-suppresses-ifn-1-pathway-signaling-in-bovine-cells-and-augments-brsv-replication
#5
Abdulrahman A Alkheraif, Christina L Topliff, Jay Reddy, Chandirasegaran Massilamany, Ruben O Donis, Gregor Meyers, Kent M Eskridge, Clayton L Kelling
Bovine viral diarrhea virus (BVDV) infection induces immunosuppression and in conjunction with bovine respiratory syncytial virus (BRSV) contributes to the bovine respiratory disease complex. Bovine turbinate cells were single or co-infected with type 2 BVDV wild-type (BVDV2-wt), its dysfunctional N(pro) mutant (BVDV2-E), and/or BRSV. BVDV2-E significantly up-regulated PKR, IRF-7, TBK-1, IRF-3, and IFN-β mRNAs based on real-time Q-RT-PCR. BRSV-infected cells expressed significantly up-regulated PKR, IRF-3, IRF-7, and IFN-β mRNAs, whereas BVDV2-wt, but not BVDV2-E, abolished this up-regulation in co-infection...
April 19, 2017: Virology
https://www.readbyqxmd.com/read/28425034/the-molluscum-contagiosum-virus-death-effector-domain-containing-protein-mc160-rxdl-motifs-are-not-required-for-its-known-viral-immune-evasion-functions
#6
Michael Beaury, Uday Kiran Velagapudi, Sarah Weber, Cassandra Soto, Tanaji T Talele, Daniel Brian Nichols
The molluscum contagiosum virus (MCV) uses a variety of immune evasion strategies to antagonize host immune responses. Two MCV proteins, MC159 and MC160, contain tandem death effector domains (DEDs). They are reported to inhibit innate immune signaling events such as NF-κB and IRF3 activation, and apoptosis. The RxDL motif of MC159 is required for inhibition of both apoptosis and NF-κB activation. However, the role of the conserved RxDL motif in the MC160 DEDs remained unknown. To answer this question, we performed alanine mutations to neutralize the arginine and aspartate residues present in the MC160 RxDL in both DED1 and DED2...
April 20, 2017: Virus Genes
https://www.readbyqxmd.com/read/28424327/rig-i-mavs-and-sting-signaling-promote-gut-integrity-during-irradiation-and-immune-mediated-tissue-injury
#7
Julius C Fischer, Michael Bscheider, Gabriel Eisenkolb, Chia-Ching Lin, Alexander Wintges, Vera Otten, Caroline A Lindemans, Simon Heidegger, Martina Rudelius, Sébastien Monette, Kori A Porosnicu Rodriguez, Marco Calafiore, Sophie Liebermann, Chen Liu, Stefan Lienenklaus, Siegfried Weiss, Ulrich Kalinke, Jürgen Ruland, Christian Peschel, Yusuke Shono, Melissa Docampo, Enrico Velardi, Robert R Jenq, Alan M Hanash, Jarrod A Dudakov, Tobias Haas, Marcel R M van den Brink, Hendrik Poeck
The molecular pathways that regulate the tissue repair function of type I interferon (IFN-I) during acute tissue damage are poorly understood. We describe a protective role for IFN-I and the RIG-I/MAVS signaling pathway during acute tissue damage in mice. Mice lacking mitochondrial antiviral-signaling protein (MAVS) were more sensitive to total body irradiation- and chemotherapy-induced intestinal barrier damage. These mice developed worse graft-versus-host disease (GVHD) in a preclinical model of allogeneic hematopoietic stem cell transplantation (allo-HSCT) than did wild-type mice...
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28424289/disruption-of-mda5-mediated-innate-immune-responses-by-the-3c-proteins-of-coxsackievirus-a16-coxsackievirus-a6-and-enterovirus-d68
#8
Yajuan Rui, Jiaming Su, Hong Wang, Junliang Chang, Shaohua Wang, Wenwen Zheng, Yong Cai, Wei Wei, James T Gordy, Richard Markham, Wei Kong, Wenyan Zhang, Xiao-Fang Yu
Coxsackievirus A16 (CV-A16), A6 (CV-A6), and enterovirus D68 (EV-D68) belong to the Picornaviridae family and are major causes of hand, foot, and mouth disease (HFMD) and pediatric respiratory disease worldwide. The biological characteristics of these viruses, especially their interplay with the host innate immune system, have not been well investigated. In this study, we discovered that the 3C(pro) proteins from CV-A16, CV-A6, and EV-D68 bind MDA5 and inhibit its interaction with MAVS. Consequently, MDA5-triggered type I IFN signaling in the RLR pathway was blocked by CV-A16, CV-A6, and EV-D68 3C(pro) Furthermore, CV-A16, CV-A6, and EV-D68 3C(pro) all cleave TAK1, resulting in inhibition of NF-κB activation, a host response also critical for toll-like receptor (TLR) mediated signaling...
April 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28418930/the-innate-immunity-of-guinea-pigs-against-highly-pathogenic-avian-influenza-virus-infection
#9
Kun Zhang, Wei Wei Xu, Zhaowei Zhang, Jing Liu, Jing Li, Lijuan Sun, Weiyang Sun, Peirong Jiao, Xiaoyu Sang, Zhiguang Ren, Zhijun Yu, Yuanguo Li, Na Feng, Tiecheng Wang, Hualei Wang, Songtao Yang, Yongkun Zhao, Xuemei Zhang, Peter R Wilker, WenJun Liu, Ming Liao, Hualan Chen, Yuwei Gao, Xianzhu Xia
H5N1 avian influenza viruses are a major pandemic concern. In contrast to the highly virulent phenotype of H5N1 in humans and many animal models, guinea pigs do not typically display signs of severe disease in response to H5N1 virus infection. Here, proteomic and transcriptional profiling were applied to identify host factors that account for the observed attenuation of A/Tiger/Harbin/01/2002 (H5N1) virulence in guinea pigs. RIG-I and numerous interferon stimulated genes were among host proteins with altered expression in guinea pig lungs during H5N1 infection...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418387/mitochondria-are-the-powerhouses-of-immunity
#10
REVIEW
Evanna L Mills, Beth Kelly, Luke A J O'Neill
Recent evidence indicates that mitochondria lie at the heart of immunity. Mitochondrial DNA acts as a danger-associated molecular pattern (DAMP), and the mitochondrial outer membrane is a platform for signaling molecules such as MAVS in RIG-I signaling, and for the NLRP3 inflammasome. Mitochondrial biogenesis, fusion and fission have roles in aspects of immune-cell activation. Most important, Krebs cycle intermediates such as succinate, fumarate and citrate engage in processes related to immunity and inflammation, in both innate and adaptive immune cells...
April 18, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28418037/mitochondrial-c11orf83-is-a-potent-antiviral-protein-independent-of-interferon-production
#11
Yun Yang, Shaoquan Xiong, Bei Cai, Hui Luo, E Dong, Qiqi Li, Gaili Ji, Chengjian Zhao, Yanjun Wen, Yuquan Wei, Hanshuo Yang
Mitochondria have a central position in innate immune response via the adaptor protein MAVS in mitochondrial outer membrane to limit viral replication by inducing interferon production. Here, we reported that C11orf83, a component of complex III of electronic transfer chain in mitochondrial inner membrane, was a potent antiviral protein independent of interferon production. C11orf83 expression significantly increased in response to viral infection, and endows cells with stronger capability of inhibiting viral replication...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28410483/contributions-of-cd8-t-cells-to-the-pathogenesis-of-mouse-adenovirus-type-1-respiratory-infection
#12
Caitlyn T Molloy, Jennifer S Andonian, Harrison M Seltzer, Megan C Procario, Michael E Watson, Jason B Weinberg
CD8 T cells are key components of the immune response to viruses, but their roles in the pathogenesis of adenovirus respiratory infection have not been characterized. We used mouse adenovirus type 1 (MAV-1) to define CD8 T cell contributions to the pathogenesis of adenovirus respiratory infection. CD8 T cell deficiency in β2m(-/-) mice had no effect on peak viral replication in lungs, but clearance of virus was delayed in β2m(-/-) mice. Virus-induced weight loss and increases in bronchoalveolar lavage fluid total protein, IFN-γ, TNF-α, IL-10, CCL2, and CCL5 concentrations were less in β2m(-/-) mice than in controls...
April 11, 2017: Virology
https://www.readbyqxmd.com/read/28410401/ripk3-interacts-with-mavs-to-regulate-type-i-ifn-mediated-immunity-to-influenza-a-virus-infection
#13
Jeffrey Downey, Erwan Pernet, François Coulombe, Benoit Allard, Isabelle Meunier, Joanna Jaworska, Salman Qureshi, Donald C Vinh, James G Martin, Philippe Joubert, Maziar Divangahi
The type I interferon pathway plays a critical role in both host defense and tolerance against viral infection and thus requires refined regulatory mechanisms. RIPK3-mediated necroptosis has been shown to be involved in anti-viral immunity. However, the exact role of RIPK3 in immunity to Influenza A Virus (IAV) is poorly understood. In line with others, we, herein, show that Ripk3-/- mice are highly susceptible to IAV infection, exhibiting elevated pulmonary viral load and heightened morbidity and mortality...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28405612/microrna-125a-and-b-inhibit-a20-and-mavs-to-promote-inflammation-and-impair-antiviral-response-in-copd
#14
Alan C-Y Hsu, Kamal Dua, Malcolm R Starkey, Tatt-Jhong Haw, Prema M Nair, Kristy Nichol, Nathan Zammit, Shane T Grey, Katherine J Baines, Paul S Foster, Philip M Hansbro, Peter A Wark
Influenza A virus (IAV) infections lead to severe inflammation in the airways. Patients with chronic obstructive pulmonary disease (COPD) characteristically have exaggerated airway inflammation and are more susceptible to infections with severe symptoms and increased mortality. The mechanisms that control inflammation during IAV infection and the mechanisms of immune dysregulation in COPD are unclear. We found that IAV infections lead to increased inflammatory and antiviral responses in primary bronchial epithelial cells (pBECs) from healthy nonsmoking and smoking subjects...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28395147/acute-effect-of-stretching-modalities-on-global-coordination-and-kicking-accuracy-in-12-13year-old-soccer-players
#15
Mohamed Frikha, Mohammad S Derbel, Nesrine Chaâri, Adnene Gharbi, Karim Chamari
The aim of the study was to compare the effect of stretching procedures on global coordination and accuracy in instep soccer kicks achieved in different stress conditions. Twenty male young soccer players completed the global coordination test (GC), the instep kicking accuracy test in free (FKA) and in time-pressure (TPKA) conditions, either after static (SS), dynamic (DS), ballistic (BS) or no-stretching (CTR) protocols, on nonconsecutive days and in a randomized order. After performing a 5min standardized intensity jogging (70% of MAV), followed by stretching exercises for 10min, each participant completed, successively, the GC, FKA and TPKA tests...
April 7, 2017: Human Movement Science
https://www.readbyqxmd.com/read/28394926/gp73-represses-host-innate-immune-response-to-promote-virus-replication-by-facilitating-mavs-and-traf6-degradation
#16
Xuewu Zhang, Chengliang Zhu, Tianci Wang, Hui Jiang, Yahui Ren, Qi Zhang, Kailang Wu, Fang Liu, Yingle Liu, Jianguo Wu
Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases and hepatocellular carcinoma (HCC) and Golgi protein 73 (GP73) is a serum biomarker for liver diseases and HCC. However, the mechanism underlying GP73 regulates HCV infection is largely unknown. Here, we revealed that GP73 acts as a novel negative regulator of host innate immunity to facilitate HCV infection. GP73 expression is activated and correlated with interferon-beta (IFN-β) production during HCV infection in patients' serum, primary human hepatocytes (PHHs) and human hepatoma cells through mitochondrial antiviral signaling protein (MAVS), TNF receptor-associated factor 6 (TRAF6) and mitogen-activated protein kinase kinase/extracellular regulated protein kinase (MEK/ERK) pathway...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28392570/human-t-cell-lymphotropic-virus-type-1-and-its-oncogenesis
#17
REVIEW
Lan-Lan Zhang, Jing-Yun Wei, Long Wang, Shi-le Huang, Ji-Long Chen
Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL), a rapidly progressing clonal malignancy of CD4+ T lymphocytes. Exploring the host-HTLV-1 interactions and the molecular mechanisms underlying HTLV-1-mediated tumorigenesis is critical for developing efficient therapies against the viral infection and associated leukemia/lymphoma. It has been demonstrated to date that several HTLV-1 proteins play key roles in the cellular transformation and immortalization of infected T lymphocytes...
April 10, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28362255/ribonuclease-l-mediates-the-cell-lethal-phenotype-of-double-stranded-rna-editing-enzyme-adar1-deficiency-in-a-human-cell-line
#18
Yize Li, Shuvojit Banerjee, Stephen A Goldstein, Beihua Dong, Christina Gaughan, Sneha Rath, Jesse Donovan, Alexei Korennykh, Robert H Silverman, Susan R Weiss
ADAR1 isoforms are adenosine deaminases that edit and destabilize double-stranded RNA reducing its immunostimulatory activities. Mutation of ADAR1 leads to a severe neurodevelopmental and inflammatory disease of children, Aicardi-Goutiéres syndrome. In mice, Adar1 mutations are embryonic lethal but are rescued by mutation of the Mda5 or Mavs genes, which function in IFN induction. However, the specific IFN regulated proteins responsible for the pathogenic effects of ADAR1 mutation are unknown. We show that the cell-lethal phenotype of ADAR1 deletion in human lung adenocarcinoma A549 cells is rescued by CRISPR/Cas9 mutagenesis of the RNASEL gene or by expression of the RNase L antagonist, murine coronavirus NS2 accessory protein...
March 31, 2017: ELife
https://www.readbyqxmd.com/read/28356916/spasmolytic-and-antibacterial-activity-of-two-citrus-sinensis-osbeck-varieties-cultivated-in-mexico
#19
Amanda Sánchez-Recillas, Ana Ly Arroyo-Herrera, Jesús Alfredo Araujo-León, Emanuel Hernández Núñez, Rolffy Ortiz Andrade
Antibacterial activity on ATCC strains of Escherichia coli, Salmonella enterica, Salmonella enteritidis, and Salmonella choleraesuis and spasmolytic effect on contraction on rat ileum trips were determinate. Eight organic extracts (hexanic and methanolic) of albedo (mesocarp) and flavedo (pericarp) of two varieties (Valencian and National) of Citrus sinensis (L.) Osbeck of Yucatán, México, were studied. Additionally, chromatographic fingerprints were obtained and correlated with their pharmacological effects...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28338528/perceptual-mechanical-and-electromyographic-responses-to-different-relative-loads-in-the-parallel-squat
#20
Mark Chapman, Eneko Larumbe-Zabala, Mark Gosss-Sampson, Mark Colpus, N Travis Triplett, Fernando Naclerio
The effectiveness of the OMNI-RES (0-10) and the electromyographic signal for monitoring changes in the movement velocity was examined during a set to muscular failure using different percentages of one repetition maximum (1RM) in the parallel squat exercise (PSQ). Twelve males (26.3 ± 5.8 years) were evaluated on eight separate days with 48 hours of rest between sessions. After determining the 1RM value, participants underwent seven tests until achieving muscular failure with the following percentage ranges: 30 to <40%; 40 to <50%, 50 to <60%, 60% to <70%, 70 to <80%, 80 to <90% and >90%...
March 23, 2017: Journal of Strength and Conditioning Research
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