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https://www.readbyqxmd.com/read/28202761/the-long-noncoding-rna-neat1-exerts-anti-hantaviral-effects-by-acting-as-a-positive-feedback-for-rig-i-signaling
#1
Hongwei Ma, Peijun Han, Wei Ye, Hesong Chen, Xuyang Zheng, Linfeng Cheng, Liang Zhang, Lan Yu, Xing'an Wu, Zhikai Xu, Yingfeng Lei, Fanglin Zhang
Hantavirus infection, which causes zoonotic diseases with a high mortality rate in humans, has long been a global public health concern. Over the past decades, accumulating evidence suggests that long noncoding RNAs (lncRNAs) play key regulatory roles in innate immunity. However, the involvement of host lncRNAs in hantaviral control remains uncharacterized. In this study, we identified the lncRNA, NEAT1, as a vital antiviral modulator. NEAT1 was dramatically upregulated after Hantaan virus (HTNV) infection, whereas its downregulation in vitro or in vivo delayed host innate immune responses and aggravated HTNV replication...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28197384/oncolytic-measles-virus-induces-tumor-necrosis-factor-related-apoptosis-inducing-ligand-trail-mediated-cytotoxicity-by-human-myeloid-and-plasmacytoid-dendritic-cells
#2
Carole Achard, Jean-Baptiste Guillerme, Daniela Bruni, Nicolas Boisgerault, Chantal Combredet, Frédéric Tangy, Nolwenn Jouvenet, Marc Grégoire, Jean-François Fonteneau
Attenuated measles virus (MV) is currently being evaluated in clinical trials as an oncolytic therapeutic agent. Originally used for its lytic activity against tumor cells, it is now admitted that the effectiveness of MV also lies in its ability to initiate antitumor immune responses through the activation of dendritic cells (DCs). In this study, we investigated the capacity of oncolytic MV to convert human blood myeloid CD1c(+) DCs and plasmacytoid DCs (pDCs) into cytotoxic effectors. We found that MV induces the expression of the cytotoxic protein TNF-related apoptosis-inducing ligand (TRAIL) on the surface of DCs...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28195391/rig-i-is-a-key-antiviral-interferon-stimulated-gene-against-hepatitis-e-virus-dispensable-of-interferon-production
#3
Lei Xu, Wenshi Wang, Yunlong Li, Xinying Zhou, Yuebang Yin, Yijin Wang, Robert A de Man, Luc J W van der Laan, Fen Huang, Nassim Kamar, Maikel P Peppelenbosch, Qiuwei Pan
: Interferons (IFNs) are broad antiviral cytokines that exert their function by inducing the transcription of hundreds of interferon-stimulated genes (ISGs). However, little is known about the antiviral potential of these cellular effectors on hepatitis E virus (HEV) infection, the leading cause of acute hepatitis globally. In this study, we profiled the antiviral potential of a panel of important human ISGs on HEV replication in cell culture models by overexpression of individual ISG...
February 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28194021/type-i-ifn-augments-il-27-dependent-trim25-expression-to-inhibit-hbv-replication
#4
Guangyun Tan, Qingfei Xiao, Hongxiao Song, Feng Ma, Fengchao Xu, Di Peng, Na Li, Xiaosong Wang, Junqi Niu, Pujun Gao, F Xiao-Feng Qin, Genhong Cheng
Hepatitis B virus (HBV) can cause chronic hepatitis B, which may lead to cirrhosis and liver cancer. Type I interferon (IFN) is an approved drug for the treatment of chronic hepatitis B. However, the fundamental mechanisms of antiviral action by type I IFN and the downstream signaling pathway are unclear. TRIM25 is an IFN-stimulated gene (ISG) that has an important role in RIG-I ubiquitination and activation. Whether TRIM25 is induced in liver cells by type I IFN to mediate anti-HBV function remains unclear...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28191486/rigulation-of-sting-expression-at-the-crossroads-of-viral-rna-and-dna-sensing-pathways
#5
Yiliu Liu, Rongtuan Lin, David Olagnier
The innate immune sensing of pathogens is important for host to mount defensive responses. STING has emerged in recent years as a critical signaling adaptor in the immune response to cytosolic DNA and RNA derived from pathogens. Liu et al. (2016) demonstrate that the RIG-I-dependent RNA sensing signaling induces STING expression via a TNF-α and IFN-α synergy. The up-regulation of STING is vital for 5'pppRNA restriction of HSV, a DNA virus that infects humans and causes herpes, in vitro and in vivo. This study provides new insights into the cross talk between DNA and RNA pathogen-sensing systems via the control of STING...
January 1, 2017: Inflammation and Cell Signaling
https://www.readbyqxmd.com/read/28181036/ddx50-inhibits-the-replication-of-dengue-virus-2-by-upregulating-ifn-%C3%AE-production
#6
Peijun Han, Wei Ye, Xin Lv, Hongwei Ma, Daihui Weng, Yangchao Dong, Linfeng Cheng, Hesong Chen, Liang Zhang, Zhikai Xu, Yingfeng Lei, Fanglin Zhang
Dengue virus (DENV) infects approximately 390 million people per year, and each of the four DENV serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) is capable of causing infection. At present, there is no antiviral drug available for the treatment of DENV. Several DExD/H-box helicases have been shown to be involved in the antiviral immune response or viral replication. In the present study, we investigated the role of DDX50 in DENV-2 RNA replication. Our data showed that the level of DENV-2 RNA increased in DDX50 knockdown cells during an early stage of viral infection and decreased in DDX50-overexpressing cells...
February 8, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28180316/selective-rna-targeting-and-regulated-signaling-by-rig-i-is-controlled-by-coordination-of-rna-and-atp-binding
#7
Megan E Fitzgerald, David C Rawling, Olga Potapova, Xiaoming Ren, Andrew Kohlway, Anna Marie Pyle
No abstract text is available yet for this article.
February 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28176867/primary-macrophages-and-j774-cells-respond-differently-to-infection-with-mycobacterium-tuberculosis
#8
Nuria Andreu, Jody Phelan, Paola F de Sessions, Jacqueline M Cliff, Taane G Clark, Martin L Hibberd
Macrophages play an essential role in the early immune response to Mycobacterium tuberculosis and are the cell type preferentially infected in vivo. Primary macrophages and macrophage-like cell lines are commonly used as infection models, although the physiological relevance of cell lines, particularly for host-pathogen interaction studies, is debatable. Here we use high-throughput RNA-sequencing to analyse transcriptome dynamics of two macrophage models in response to M. tuberculosis infection. Specifically, we study the early response of bone marrow-derived mouse macrophages and cell line J774 to infection with live and γ-irradiated (killed) M...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28159912/identification-of-tbk1-complexes-required-for-the-phosphorylation-of-irf3-and-the-production-of-interferon-b
#9
Siddharth Bakshi, Jordan Taylor, Sam Strickson, Thomas Macartney, Philip Cohen
The double-stranded RNA mimetic poly(I:C) and LPS activate Toll-like Receptor 3 (TLR3) and TLR4, respectively, triggering the activation of TANK-Binding Kinase 1 (TBK1) complexes, the phosphorylation of Interferon Regulatory Factor 3 (IRF3) and transcription of the Interferon b (IFNb) gene. Here, we demonstrate that the TANK-TBK1 and Optineurin (OPTN)-TBK1 complexes control this pathway. The poly(I:C)- or LPS-stimulated phosphorylation of IRF3 at Ser396 and production of IFNb were greatly reduced in bone-marrow-derived macrophages (BMDM) from TANK knock-out (KO) mice crossed to knock-in mice-expressing the ubiquitin-binding-defective OPTN[D477N] mutant...
February 3, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28152074/multiple-ubxn-family-members-inhibit-retrovirus-and-lentivirus-production-and-canonical-nf%C3%AE%C2%BA%C3%AE-signaling-by-stabilizing-i%C3%AE%C2%BAb%C3%AE
#10
Yani Hu, Kaitlin O'Boyle, Jim Auer, Sagar Raju, Fuping You, Penghua Wang, Erol Fikrig, Richard E Sutton
UBXN proteins likely participate in the global regulation of protein turnover, and we have shown that UBXN1 interferes with RIG-I-like receptor (RLR) signaling by interacting with MAVS and impeding its downstream effector functions. Here we demonstrate that over-expression of multiple UBXN family members decreased lentivirus and retrovirus production by several orders-of-magnitude in single cycle assays, at the level of long terminal repeat-driven transcription, and three family members, UBXN1, N9, and N11 blocked the canonical NFκB pathway by binding to Cullin1 (Cul1), inhibiting IκBα degradation...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28152048/zika-virus-antagonizes-type-i-interferon-responses-during-infection-of-human-dendritic-cells
#11
James R Bowen, Kendra M Quicke, Mohan S Maddur, Justin T O'Neal, Circe E McDonald, Nadia B Fedorova, Vinita Puri, Reed S Shabman, Bali Pulendran, Mehul S Suthar
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that is causally linked to severe neonatal birth defects, including microcephaly, and is associated with Guillain-Barre syndrome in adults. Dendritic cells (DCs) are an important cell type during infection by multiple mosquito-borne flaviviruses, including dengue virus, West Nile virus, Japanese encephalitis virus, and yellow fever virus. Despite this, the interplay between ZIKV and DCs remains poorly defined. Here, we found human DCs supported productive infection by a contemporary Puerto Rican isolate with considerable variability in viral replication, but not viral binding, between DCs from different donors...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28150518/chloroquine-attenuates-tlr3-ifn-%C3%AE-signaling-in-cultured-normal-human-mesangial-cells-a-possible-protective-effect-against-renal-damage-in-lupus-nephritis
#12
Tadaatsu Imaizumi, Ryo Hayakari, Tomoh Matsumiya, Hidemi Yoshida, Kazushi Tsuruga, Shojiro Watanabe, Shogo Kawaguchi, Hiroshi Tanaka
BACKGROUND: Chloroquine has been reported to protect against renal damage in lupus nephritis (LN), however, its detailed mechanism in glomerular inflammation remains unclear. Upregulation of the type I interferon (IFN) system plays a pivotal role in LN pathogenesis, therefore, we examined whether chloroquine inhibits Toll-like receptor 3 (TLR3)/IFN-β signaling in cultured normal human mesangial cells (MCs). METHODS: We examined chloroquine effect on the representative TLR3/IFN-β signaling axis, TLR3/IFN-β/retinoic acid-inducible gene-I (RIG-I)/CCL5 in MCs treated with polyinosinic-polycytidylic acid (poly IC), a synthetic viral dsRNA analog and analyzed the expression of these molecules using reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay...
February 2, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28148787/sars-coronavirus-nucleocapsid-inhibits-type-i-interferon-production-by-interfering-with-trim25-mediated-rig-i-ubiquitination
#13
Yong Hu, Wei Li, Ting Gao, Yan Cui, Yanwen Jin, Ping Li, Qingjun Ma, Xuan Liu, Cheng Cao
: Severe acute respiratory syndrome (SARS) is a respiratory disease caused by a coronavirus (SARS-CoV) that is characterized by atypical pneumonia. The nucleocapsid protein (N protein) of SARS-CoV plays an important role in inhibition of type I interferon (IFN) production via an unknown mechanism. In this study, the SARS-CoV N protein was found to bind to the SPRY domain of the tripartite motif protein 25 (TRIM25) E3 ubiquitin ligase, thereby interfering with the association between TRIM25 and retinoic acid-inducible gene I (RIG-I) and inhibiting TRIM25-mediated RIG-I ubiquitination and activation...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28138020/the-type-ii-secretion-system-of-legionella-pneumophila-dampens-the-myd88-and-tlr2-signaling-pathway-in-infected-human-macrophages
#14
Celeste A Mallama, Kessler McCoy-Simandle, Nicholas P Cianciotto
Previously, we reported that mutants of L. pneumophila lacking a type II secretion (T2S) system elicit higher levels of cytokines (e.g., IL-6) following infection of U937 cells, a human macrophage-like cell line. We now show that this effect of T2S is also manifest upon infection of human THP-1 cell macrophages and peripheral blood monocytes but does not occur during infection of murine macrophages. Supporting the hypothesis that T2S acts to dampen the triggering of an innate immune response, we observed that the mitogen-activated protein kinase (MAPK) and nuclear transcription factor kappa-B (NF-κB) pathways are more highly stimulated upon infection with the T2S mutant compared to wild-type...
January 30, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28132841/phosphorylation-dependent-feedback-inhibition-of-rig-i-by-dapk1-identified-by-kinome-wide-sirna-screening
#15
Joschka Willemsen, Oliver Wicht, Julia C Wolanski, Nina Baur, Sandra Bastian, Darya A Haas, Petr Matula, Bettina Knapp, Laurène Meyniel-Schicklin, Chen Wang, Ralf Bartenschlager, Volker Lohmann, Karl Rohr, Holger Erfle, Lars Kaderali, Joseph Marcotrigiano, Andreas Pichlmair, Marco Binder
Cell-autonomous induction of type I interferon must be stringently regulated. Rapid induction is key to control virus infection, whereas proper limitation of signaling is essential to prevent immunopathology and autoimmune disease. Using unbiased kinome-wide RNAi screening followed by thorough validation, we identified 22 factors that regulate RIG-I/IRF3 signaling activity. We describe a negative-feedback mechanism targeting RIG-I activity, which is mediated by death associated protein kinase 1 (DAPK1). RIG-I signaling triggers DAPK1 kinase activation, and active DAPK1 potently inhibits RIG-I stimulated IRF3 activity and interferon-beta production...
February 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28119144/identification-ontogeny-and-expression-analysis-of-a-novel-laboratory-of-genetics-and-physiology-2-lgp2-transcript-in-asian-seabass-lates-calcarifer
#16
Anutosh Paria, A Deepika, K Sreedharan, M Makesh, Aparna Chaudhari, C S Purushothaman, K V Rajendran
LGP2 (laboratory of genetics and physiology 2) is an important member of the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), which plays a significant role in antiviral innate immunity. In this study, we have cloned the full-length cDNA sequence of LGP2 from Asian seabass, Lates calcarifer (AsLGP2). The complete AsLGP2 cDNA sequence consisted of 2586 nucleotides encoding a putative protein of 681 amino acids with a molecular mass of 77.6 kDa. From the AsLGP2 protein, four different conserved domains were predicted: a DExDc (DEAD/DEAH box helicase domain), a bacterial type III restriction enzyme domain (RES III), a HELICc (Helicase superfamily c-terminal domain and a RIG-I_C-RD (RIG-I C-terminal regulatory domain)...
January 21, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28114392/identification-of-5-methoxy-2-diformylmethylidene-3-3-dimethylindole-as-an-anti-influenza-a-virus-agent
#17
Ming Cheang Tan, Wan Ying Wong, Wei Lun Ng, Kok Siong Yeo, Taznim Begam Mohd Mohidin, Yat-Yuen Lim, Fadhil Lafta, Hapipah Mohd Ali, Chee-Kwee Ea
Influenza virus is estimated to cause 3-5 million severe complications and about 250-500 thousand deaths per year. Different kinds of anti-influenza virus drugs have been developed. However, the emergence of drug resistant strains has presented a big challenge for efficient antiviral therapy. Indole derivatives have been shown to exhibit both antiviral and anti-inflammatory activities. In this study, we adopted a cell-based system to screen for potential anti-IAV agents. Four indole derivatives (named 525A, 526A, 527A and 528A) were subjected to the antiviral screening, of which 526A was selected for further investigation...
2017: PloS One
https://www.readbyqxmd.com/read/28109979/interferon-ifn-induced-protein-35-ifi35-negatively-regulates-ifn-%C3%AE-phosphorylated-stat1-rig-i-cxcl10-ccl5-axis-in-u373mg-astrocytoma-cells-treated-with-polyinosinic-polycytidylic-acid
#18
Kyogo Shirai, Taku Shimada, Hidemi Yoshida, Ryo Hayakari, Tomoh Matsumiya, Kunikazu Tanji, Manabu Murakami, Hiroshi Tanaka, Tadaatsu Imaizumi
Interferon (IFN)-stimulated genes (ISGs) exert multiple functions in immune system. IFN-induced protein 35 (IFI35) is a member of ISGs, and has been suggested to regulate innate immune reaction. However, the physiological functions and pathological roles of IFI35 in the central nervous system are not characterized well. In the present study, we found that the expression of IFI35 was induced by a Toll-like receptor 3 (TLR3) ligand polyinosinic-polycytidylic acid (poly IC) in U373MG human astrocytoma cells. Knockdown of IFI35 using RNA interference resulted in increased expression of IFN-β, phosphorylated STAT1 (P-STAT1), retinoic acid-inducible gene-I (RIG-I), CXCL10 and CCL5 induced by poly IC...
January 18, 2017: Brain Research
https://www.readbyqxmd.com/read/28109007/retinoic-acid-inducible-gene-i-rig-i-like-receptors-rlrs-in-fish-current-knowledge-and-future-perspectives
#19
REVIEW
Shan Nan Chen, Peng Fei Zou, Pin Nie
Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are found conservatively present in teleost fish. All three members, RIG-I, MDA5 and LGP2 together with the downstream molecules such as MITA, TRAF3 and TBK1 have been identified in a range of fish species. However, it is a bit unexpected that RIG-I has not been reported in fish of Acanthopterygii, and it would be important to clarify the presence and role of RIG-I gene in a broad range of taxa in Teleostei. RLRs in fish can be induced in vivo and in vitro by viral pathogens as well as synthetic double-stranded RNA (dsRNA), poly(I:C), leading to the production of type I IFNs and the expression of IFN stimulated genes (ISGs)...
January 20, 2017: Immunology
https://www.readbyqxmd.com/read/28100701/self-cytoplasmic-dna-upregulates-the-mutator-enzyme-apobec3a-leading-to-chromosomal-dna-damage
#20
Rodolphe Suspène, Bianka Mussil, Hélène Laude, Vincent Caval, Noémie Berry, Mohamed S Bouzidi, Valérie Thiers, Simon Wain-Hobson, Jean-Pierre Vartanian
Foreign and self-cytoplasmic DNA are recognized by numerous DNA sensor molecules leading to the production of type I interferons. Such DNA agonists should be degraded otherwise cells would be chronically stressed. Most human APOBEC3 cytidine deaminases can initiate catabolism of cytoplasmic mitochondrial DNA. Using the human myeloid cell line THP-1 with an interferon inducible APOBEC3A gene, we show that cytoplasmic DNA triggers interferon α and β production through the RNA polymerase III transcription/RIG-I pathway leading to massive upregulation of APOBEC3A By catalyzing C→U editing in single stranded DNA fragments, the enzyme prevents them from re-annealing so attenuating the danger signal...
January 18, 2017: Nucleic Acids Research
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