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https://www.readbyqxmd.com/read/28815217/deletion-of-cytoplasmic-double-stranded-rna-sensors-does-not-uncover-viral-small-interfering-rna-production-in-human-cells
#1
Susan Schuster, Lotte E Tholen, Gijs J Overheul, Frank J M van Kuppeveld, Ronald P van Rij
Antiviral immunity in insects and plants is mediated by the RNA interference (RNAi) pathway in which viral long double-stranded RNA (dsRNA) is processed into small interfering RNAs (siRNAs) by Dicer enzymes. Although this pathway is evolutionarily conserved, its involvement in antiviral defense in mammals is the subject of debate. In vertebrates, recognition of viral RNA induces a sophisticated type I interferon (IFN)-based immune response, and it has been proposed that this response masks or inhibits antiviral RNAi...
July 2017: MSphere
https://www.readbyqxmd.com/read/28795873/anti-mda5-positive-dermatomyositis-an-emerging-entity-with-a-variable-clinical-presentation
#2
V Ortiz-Santamaria, A Babot, C Ferrer
No abstract text is available yet for this article.
August 10, 2017: Scandinavian Journal of Rheumatology
https://www.readbyqxmd.com/read/28794402/dec1-negatively-regulates-the-expression-of-cxcl10-and-ccl5-induced-by-poly-ic-in-normal-human-mesangial-cells
#3
Qiang Liu, Tadaatsu Imaizumi, Keishu Murakami, Hiroshi Tanaka, Yunyan Wu, Tadashi Yoshizawa, Satoko Morohashi, Hiroko Seino, Hiroshi Kijima
The functions of differentiated embryonic chondrocyte gene (DEC) 1, a basic helix-loop-helix (bHLH) transcription factor, have been reported to be associated with the regulation of mammalian circadian rhythms, differentiation of chondrocytes and skeletal muscles, apoptosis, hypoxia-induced reactions and epithelial mesenchymal transition. Our previous report showed that another bHLH transcription factor DEC2 constitutes a negative feedback loop in Toll-like receptor 3 (TLR3)/interferon (IFN)-β-mediated inflammatory responses in human mesangial cells...
2017: Biomedical Research
https://www.readbyqxmd.com/read/28794024/highly-pathogenic-new-world-arenavirus-infection-activates-the-pattern-recognition-receptor-pkr-without-attenuating-virus-replication-in-human-cells
#4
Cheng Huang, Olga A Kolokoltsova, Elizabeth J Mateer, Takaaki Koma, Slobodan Paessler
The arenavirus family consists of several highly pathogenic viruses including the Old World (OW) arenavirus Lassa fever virus (LASV) and the New World (NW) Junín virus (JUNV) and Machupo virus (MACV). Host response to infection by these pathogenic arenaviruses is distinct in many aspects. NW JUNV and MACV infections readily induce an IFN response in human cells, while OW LASV infection usually triggers an undetectable or weak IFN response. JUNV induces IFN response through RIG-I, suggesting that the host non-self RNA sensor readily detects JUNV viral RNAs during infection and activates IFN response...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28768856/non-encapsidated-5-copy-back-defective-interfering-genomes-produced-by-recombinant-measles-viruses-are-recognized-by-rig-i-and-lgp2-but-not-mda5
#5
Marie Mura, Chantal Combredet, Valérie Najburg, Raul Y Sanchez David, Frédéric Tangy, Anastassia V Komarova
Attenuated Measles virus (MV) is one of the most effective and safe vaccine available, making it an attractive candidate vector to prevent other infectious diseases. Yet the great capacity of this vaccine still needs to be understood at the molecular level. MV vaccine strains have different type-I interferon-inducing abilities, that partially depend on the presence of 5' copy-back defective interfering genomes (DI-RNAs). DI-RNAs are pathogen associated molecular patterns recognized by RIG-I-like receptors (RLRs: RIG-I, MDA5 and LGP2) that activate innate immune signalling and shape the adaptive immune response...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28760986/pum1-is-a-biphasic-negative-regulator-of-innate-immunity-genes-by-suppressing-lgp2
#6
Yonghong Liu, Linlin Qu, Yuanyuan Liu, Bernard Roizman, Grace Guoying Zhou
PUM1 is an RNA binding protein shown to regulate the stability and function of mRNAs bearing a specific sequence. We report the following: (i) A key function of PUM1 is that of a repressor of key innate immunity genes by repressing the expression of LGP2. Thus, between 12 and 48 hours after transfection of human cells with siPUM1 RNA there was an initial (phase 1) upsurge of transcripts encoding LGP2, CXCL10, IL6, and PKR. This was followed 24 hours later (phase 2) by a significant accumulation of mRNAs encoding RIG-I, SP100, MDA5, IFIT1, PML, STING, and IFNβ...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28760879/pact-facilitates-rna-induced-activation-of-mda5-by-promoting-mda5-oligomerization
#7
Pak-Yin Lui, Lok-Yin Roy Wong, Ting-Hin Ho, Shannon Wing Ngor Au, Chi-Ping Chan, Kin-Hang Kok, Dong-Yan Jin
MDA5 is a RIG-I-like cytoplasmic sensor of dsRNA and certain RNA viruses, such as encephalomyocarditis virus, for the initiation of the IFN signaling cascade in the innate antiviral response. The affinity of MDA5 toward dsRNA is low, and its activity becomes optimal in the presence of unknown cellular coactivators. In this article, we report an essential coactivator function of dsRNA-binding protein PACT in mediating the MDA5-dependent type I IFN response. Virus-induced and polyinosinic-polycytidylic acid-induced activation of MDA5 were severely impaired in PACT-knockout cells and attenuated in PACT-knockdown cells, but they were potentiated when PACT was overexpressed...
July 31, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28757363/poly-i-c-alleviates-obesity-related-pro-inflammatory-status-and-promotes-glucose-homeostasis
#8
Ying-Hui Wang, Yu-Gen Zhang
Obesity associated insulin resistance (IR) is implicated in chronic inflammation that mediated by the immune system. Imbalance between anti-inflammatory and pro-inflammatory response contributes to the origins and drivers of IR. However, cells of innate and adaptive immune system participate in the pathogenesis of IR, while glucose homeostasis related immune tolerance could be compromised high fat diet (HFD) reduced metabolic disorder. Although previous studies have demonstrated that anti-inflammatory therapy has a protective role in alleviating the pro-inflammatory status in HFD induced IR, the precise mechanism is still unclear...
July 27, 2017: Cytokine
https://www.readbyqxmd.com/read/28729212/the-influence-of-temperature-on-viral-replication-and-antiviral-related-genes-response-in-hirame-rhabdovirus-infected-flounder-paralichthys-olivaceus
#9
Jialin Zhang, Xiaoqian Tang, Xiuzhen Sheng, Jing Xing, Wenbin Zhan
Hirame rhabdovirus (HIRRV) is a rhabdovirus that causes severe disease in fish. The mortality due to HIRRV infection occurs at temperatures below 15 °C, but no mortality is observed over 20 °C. In this study, Japanese flounder (Paralichthys olivaceus) was artificially infected with the HIRRV CNPo2015 strain at 10 °C or 20 °C. Absolute quantitative real-time PCR was employed to examine the viral replication in spleens after HIRRV infection. Expression profiles of four interferon-related genes (type I IFN, Mx, ISG15, MDA5) and two proinflammatory genes (TNF-α and IL-1β) were also investigated by quantitative real-time PCR...
July 17, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28722667/assessment-of-anti-mda5-antibody-as-a-diagnostic-biomarker-in-patients-with-dermatomyositis-associated-interstitial-lung-disease-or-rapidly-progressive-interstitial-lung-disease
#10
Liubing Li, Qian Wang, Xiaoting Wen, Chenxi Liu, Chanyuan Wu, Funing Yang, Xiaofeng Zeng, Yongzhe Li
Anti-melanoma differentiation-associated protein 5 (MDA5) antibody have been found in dermatomyositis (DM)-associated interstitial lung disease (DM-ILD) and DM-associated rapidly progressive ILD (DM-RPILD). Due to the conflicting results regarding the association between anti-MDA5 antibody and DM-ILD or DM-RPILD and the diagnostic value of this antibody for DM-ILD and DM-RPILD, we performed this meta-analysis. A systematic search was performed to identify studies published to January 14, 2017. Sixteen publications with 491 DM with ILD versus 605 DM without ILD, as well as eighteen publications with 186 DM with RPILD and 790 DM without RPILD were included...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28711882/hla-drb1-alleles-as-genetic-risk-factors-for-the-development-of-anti-mda5-antibodies-in-patients-with-dermatomyositis
#11
Zhiyong Chen, Yan Wang, Masataka Kuwana, Xue Xu, Wei Hu, Xuebing Feng, Hong Wang, Akinori Kimura, Lingyun Sun
OBJECTIVE: Patients with polymyositis/dermatomyositis (PM/DM) who express anti-melanoma differentiation associated protein 5 (anti-MDA5) antibodies frequently present with interstitial lung disease (ILD). The aim of this study was to investigate the association of HLA-DRB1 with anti-MDA5 expression in PM/DM. METHODS: The frequency of DRB1 alleles was compared among 70 patients with PM, 104 patients with DM, and 400 healthy controls in a Han Chinese population. RESULTS: Frequencies of DRB1*04:01 [17...
July 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28674528/host-differences-affecting-resistance-and-susceptibility-of-the-second-generation-of-a-pekin-duck-flock-to-duck-hepatitis-a-virus-genotype-3
#12
Xiaoyan Wang, Jiaojiao Zhang, Runze Meng, Yong Jiang, Suyun Liang, Yunsheng Zhang, Ming Xie, Zhengkui Zhou, Shuisheng Hou
Earlier work suggested the possibility to anti duck hepatitis A virus genotype 3 (DHAV-3) using the resistance breeding strategy. Here, we report the creation of the second generations of a resistant Pekin duck flock (designated Z8R2) and a highly susceptible Pekin duck flock (designated Z8S2) and the investigation of their responses to DHAV-3. Experimental infection with DHAV-3 at 7 days of age resulted in a high mortality (66.3%) in 11 susceptible Z8S2 families and an extremely low mortality rate (2.67%) in 32 Z8R2 families, indicating that Z8R2 exhibits strong resistance to DHAV-3, while Z8S2 is highly susceptible to the virus...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28668260/-amyopathic-dermatomyositis-dm-with-anti-mda5-antibodies-associated-with-bullous-pemphigoid-sj%C3%A3-gren-syndrome-and-gastric-malt-lymphoma
#13
B Garcia, F Dabouz, L Pascal, M Gillard, P Modiano
BACKGROUND: The inflammatory myopathies are a heterogeneous group of muscle diseases and comprise polymyositis, dermatomyositis (DM), myopathies associated with cancers, necrotising myositis and inclusion body myositis. DM occasionally exhibits few or no muscular signs: i.e. hypomyopathic/amyopathic DM. Anti-MDA5 dermatomyositis (DM) is a rare form of dermatomyositis that is frequently amyopathic; the prognosis is linked mainly to pulmonary involvement. PATIENTS AND METHODS: A 69-year-old woman treated for mucosa-associated lymphoid tissue (MALT) gastric lymphoma was referred for a bullous eruption...
June 28, 2017: Annales de Dermatologie et de Vénéréologie
https://www.readbyqxmd.com/read/28659477/west-nile-virus-ns1-antagonizes-interferon-%C3%AE-production-by-targeting-rig-i-and-mda5
#14
Hong-Lei Zhang, Han-Qing Ye, Si-Qing Liu, Cheng-Lin Deng, Xiao-Dan Li, Pei-Yong Shi, Bo Zhang
West Nile virus (WNV) is a mosquito-borne flavivirus that causes epidemics of encephalitis and viscerotropic disease worldwide. This virus has spread rapidly and has posed significant a public health threat since the outbreak in New York City in 1999. The interferon (IFN)-mediated antiviral response represents an important component of virus-host interactions and plays an essential role in regulating viral replication. Previous studies have suggested that multifunctional non-structural proteins encoded by flaviviruses antagonize the host IFN response via various means in order to establish efficient viral replication...
June 28, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28615462/posttranslational-modification-as-a-critical-determinant-of-cytoplasmic-innate-immune-recognition
#15
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/28614378/comparative-analysis-of-virus-host-interactions-caused-by-a-virulent-and-an-attenuated-duck-hepatitis-a-virus-genotype-1
#16
Xumin Ou, Sai Mao, Jingyu Cao, Anchun Cheng, Mingshu Wang, Dekang Zhu, Shun Chen, Renyong Jia, Mafeng Liu, Kunfeng Sun, Qiao Yang, Ying Wu, Xiaoyue Chen
Because of their better immunogenicity and the improved protection they afford, live attenuated vaccines derived from serial passaging in an abnormal host are widely used to protect humans or animals from certain pathogens. Here, we used a virulent and a chicken embryo-attenuated duck hepatitis A virus genotype 1 to compare the different regulated immune responses induced by viruses with differing virulence. In this study, the attenuated strains had lower protein expression levels than the virulent strains as identified by immunohistochemistry...
2017: PloS One
https://www.readbyqxmd.com/read/28606988/recurrent-rhinovirus-infections-in-a-child-with-inherited-mda5-deficiency
#17
Ian T Lamborn, Huie Jing, Yu Zhang, Scott B Drutman, Jordan K Abbott, Shirin Munir, Sangeeta Bade, Heardley M Murdock, Celia P Santos, Linda G Brock, Evan Masutani, Emmanuel Y Fordjour, Joshua J McElwee, Jason D Hughes, Dave P Nichols, Aziz Belkadi, Andrew J Oler, Corinne S Happel, Helen F Matthews, Laurent Abel, Peter L Collins, Kanta Subbarao, Erwin W Gelfand, Michael J Ciancanelli, Jean-Laurent Casanova, Helen C Su
MDA5 is a cytosolic sensor of double-stranded RNA (ds)RNA including viral byproducts and intermediates. We studied a child with life-threatening, recurrent respiratory tract infections, caused by viruses including human rhinovirus (HRV), influenza virus, and respiratory syncytial virus (RSV). We identified in her a homozygous missense mutation in IFIH1 that encodes MDA5. Mutant MDA5 was expressed but did not recognize the synthetic MDA5 agonist/(ds)RNA mimic polyinosinic-polycytidylic acid. When overexpressed, mutant MDA5 failed to drive luciferase activity from the IFNB1 promoter or promoters containing ISRE or NF-κB sequence motifs...
July 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28605144/musculoskeletal-disease-in-mda5-related-type-i-interferonopathy-a-mendelian-mimic-of-jaccoud-s-arthropathy
#18
Luciana Martins de Carvalho, Gonza Ngoumou, Ji Woo Park, Nadja Ehmke, Nikolaus Deigendesch, Naoki Kitabayashi, Isabelle Melki, Flávio Falcäo L Souza, Andreas Tzschach, Marcello H Nogueira-Barbosa, Virgínia Ferriani, Paulo Louzada-Junior, Wilson Marques Junior, Charles M Lourenço, Denise Horn, Tilmann Kallinich, Werner Stenzel, Sun Hur, Gillian I Rice, Yanick J Crow
Objectives To define the molecular basis of a multisystem phenotype with progressive musculoskeletal disease of the hands and feet including camptodactyly, subluxation and tendon rupture reminiscent of Jaccoud's arthropathy. Methods We ascertained two families segregating an autosomal dominant phenotype encompassing musculoskeletal disease and variable additional features including psoriasis, dental abnormalities, cardiac valve involvement, glaucoma and basal ganglia calcification. We measured the expression of interferon-stimulated genes in peripheral blood and skin, and undertook targeted Sanger sequencing of the IFIH1 gene encoding the cytosolic double-stranded RNA sensor MDA5...
June 12, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28594402/arrdc4-regulates-enterovirus-71-induced-innate-immune-response-by-promoting-k63-polyubiquitination-of-mda5-through-trim65
#19
Jun Meng, Zhenyu Yao, Yaqing He, Renli Zhang, Yanwei Zhang, Xiangjie Yao, Hong Yang, Long Chen, Zhen Zhang, Hailong Zhang, Xueqin Bao, Gang Hu, Tangchun Wu, Jinquan Cheng
Enterovirus 71 (EV71) is the main causative agent of hand, foot and mouth disease (HFMD), which induces significantly elevated levels of cytokines and chemokines, leading to local or system inflammation and severe complications, whereas the underlying regulatory mechanisms and the inflammatory pathogenesis remain elusive. ARRDC4 is one member of arrestins family, having important roles in glucose metabolism and G-protein-coupled receptors (GPCRs) related physiological and pathological processes, however, the function of ARRDC4 in innate immune system is largely unknown...
June 8, 2017: Cell Death & Disease
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
#20
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)...
July 25, 2017: Oncotarget
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