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https://www.readbyqxmd.com/read/28791126/investigation-of-sphingosine-kinase-1-in-interferon-responses-during-dengue-virus-infection
#1
Amanda L Aloia, Julie K Calvert, Jennifer N Clarke, Lorena T Davies, Karla J Helbig, Stuart M Pitson, Jillian M Carr
Dengue virus (DENV) regulates sphingosine kinase (SK)-1 activity and chemical inhibition of SK1 reduces DENV infection. In primary murine embryonic fibroblasts (pMEFs) lacking SK1 however, DENV infection is enhanced and this is associated with induction of normal levels of interferon beta (IFN-β) but reduced levels of IFN-stimulated genes (ISGs). We have further investigated this link between SK1 and type I IFN responses. DENV infection downregulates cell-surface IFN-alpha receptor (IFNAR)1 in both wild-type (WT) and SK1(-)(/-) pMEF, but, consistent with poor ISG responses, shows reduced induction of phosphorylated (p)-STAT1 and key IFN regulatory factors (IRF)1 and -7 in SK1(-/-) pMEF...
July 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28768867/mechanism-of-interferon-stimulated-gene-induction-in-hiv-1-infected-macrophages
#2
Najla Nasr, Abdullateef A Alshehri, Thomas K Wright, Maryam Shahid, Bonnie M Heiner, Andrew N Harman, Rachel A Botting, Karla J Helbig, Michael R Beard, Kazuo Suzuki, Anthony D Kelleher, Paul Hertzog, Anthony L Cunningham
Viruses manipulate the complex interferon and interferon stimulated gene (ISG) system in different ways. We have previously shown that HIV inhibits type I and III interferons in its key target cells but directly stimulates a subset of >20 ISGs in macrophages and dendritic cells many of which are antiviral. Here we examined the mechanism of induction of ISGs and showed this occurred in two phases. The first phase was transient (0-24hpi) induced mainly by extracellular vesicles, and one of its component proteins HSP90α, contained within the HIV inoculum...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28768861/positive-and-negative-regulation-of-type-i-interferons-by-the-human-t-cell-leukemia-virus-antisense-protein-hbz
#3
Manraj Singh Narulla, Ahlam Alsairi, Lucie Charmier, Stephen Noonan, David Conroy, William W Hall, Noreen Sheehy
The pathogenesis of human T-cell leukemia virus type 1 (HTLV-1) is strongly linked to the viral regulatory proteins Tax1 and HBZ, whose opposing functions contribute to the clinical outcome of infection. Type I interferons α and β (IFNα and IFNβ) are key cytokines involved in innate immunity and IFNα, in combination with other antivirals, is extensively used in the treatment of HTLV-1 infection. The relationship between HTLV-1 and IFN signaling is unclear and to date the effect of HBZ on this pathway has not been examined...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28768858/human-metapneumovirus-m2-2-protein-acts-as-a-negative-regulator-of-alpha-interferon-production-by-plasmacytoid-dendritic-cells
#4
Yoshinori Kitagawa, Madoka Sakai, Mariko Funayama, Masae Itoh, Bin Gotoh
Human metapneumovirus (HMPV) has the ability to inhibit TLR7- and TLR9-dependent alpha interferon (IFN-α) production by plasmacytoid dendritic cells (pDCs). However the inhibition mechanism remains largely unknown. To identify viral proteins responsible for this inhibition, we performed a screening of HMPV open reading frames (ORFs) for their abilities to block TLR7/9-dependent signaling reconstituted in HEK293T cells by transfection with MyD88, TRAF6, IKKα, and IRF7. This screening demonstrated that the M2-2 protein was the most potent inhibitor of TLR7/9-dependent IFN-α induction...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28747667/rna-sequencing-reveals-resistance-of-tlr4-ligand-activated-microglial-cells-to-inflammation-mediated-by-the-selective-jumonji-h3k27-demethylase-inhibitor
#5
Amitabh Das, Sarder Arifuzzaman, Taeho Yoon, Sun Hwa Kim, Jin Choul Chai, Young Seek Lee, Kyoung Hwa Jung, Young Gyu Chai
Persistent microglial activation is associated with the production and secretion of various pro-inflammatory genes, cytokines and chemokines, which may initiate or amplify neurodegenerative diseases. A novel synthetic histone 3 lysine 27 (H3K27) demethylase JMJD3 inhibitor, GSK-J4, was proven to exert immunosuppressive activities in macrophages. However, a genome-wide search for GSK-J4 molecular targets has not been undertaken in microglia. To study the immuno-modulatory effects of GSK-J4 at the transcriptomic level, triplicate RNA sequencing and quantitative real-time PCR analyses were performed with resting, GSK-J4-, LPS- and LPS + GSK-J4-challenged primary microglial (PM) and BV-2 microglial cells...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747508/mutations-in-the-e2-glycoprotein-and-the-3-untranslated-region-enhance-chikungunya-virus-virulence-in-mice
#6
David W Hawman, Kathryn S Carpentier, Julie M Fox, Nicholas A May, Wes Sanders, Stephanie A Montgomery, Nathaniel J Moorman, Michael S Diamond, Thomas E Morrison
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes debilitating musculoskeletal pain and inflammation and can persist for months to years after acute infection. Although studies in humans and experimentally-infected animals suggest that CHIKV infection persists in musculoskeletal tissues, the mechanisms for this remain poorly understood. To evaluate this further, we isolated CHIKV from the serum of persistently infected Rag1(-/-) mice at day 28. When inoculated into naïve WT mice, this persistently circulating CHIKV strain displayed a capacity for earlier dissemination and greater pathogenicity compared with the parental virus...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28726298/faah-but-not-magl-inhibition-modulates-acute-tlr3-induced-neuroimmune-signaling-in-the-rat-independent-of-sex
#7
Lisa E Flannery, Rebecca J Henry, Daniel M Kerr, David P Finn, Michelle Roche
Toll-like receptor (TLR)3 is a key component of the innate immune response to viral infection. The present study firstly examined whether sex differences exist in TLR3-induced inflammatory, endocrine, and sickness responses. The data revealed that TLR3-induced expression of interferon- or NFkB-inducible genes (IFN-α/β, IP-10, or TNF-α), either peripherally (spleen) or centrally (hypothalamus), did not differ between male and female rats, with the exception of TLR3-induced IFN-α expression in the spleen of female, but not male, rats 8 hr post TLR3 activation...
July 20, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28719617/microrna-155-deficiency-leads-to-decreased-autoantibody-levels-and-reduced-severity-of-nephritis-and-pneumonitis-in-pristane-induced-lupus
#8
Harald Leiss, Wilhelm Salzberger, Barbara Jacobs, Irina Gessl, Nicolas Kozakowski, Stephan Blüml, Antonia Puchner, Attila Kiss, Bruno K Podesser, Josef S Smolen, Georg H Stummvoll
OBJECTIVE: We herein examine the role of endogenous miR155 in the development of systemic manifestations in pristane induced lupus. MATERIALS AND METHODS: Systemic lupus in miR155-deficient and wild type mice was induced upon injection of pristane and analyzed after 8 months, PBS-injected mice served as controls. Glomerulonephritis and pneumonitis were quantified using the kidney biopsy score and a newly adapted histomorphometric image analysis system; lung tissue was further analyzed by tissue cytometry...
2017: PloS One
https://www.readbyqxmd.com/read/28712115/expression-of-interferon-regulatory-factor-7-correlates-with-the-expression-of-epstein-barr-virus-latent-membrane-protein-1-and-cervical-lymph-node-metastasis-in-nasopharyngeal-cancer
#9
Satoru Kondo, Kazuhira Endo, Naohiro Wakisaka, Mitsuharu Aga, Makoto Kano, Noriko Seishima, Tomoko Imoto, Eiji Kobayashi, Makiko Moriyama-Kita, Yosuke Nakanishi, Shigeyuki Murono, Joseph S Pagano, Tomokazu Yoshizaki
Interferon regulatory factor 7 (IRF7) has oncogenic properties in several malignancies such as Epstein-Barr virus (EBV)-associated lymphoma. However, there is no evidence whether IRF7 is associated with the oncogenesis of nasopharyngeal cancer (NPC), the pathogenesis of which is closely associated with EBV. Herein, we report that expression of IRF7 was increased in normal nasopharyngeal cells that expressed the EBV principal oncoprotein, latent membrane protein 1 (LMP1). In addition, IRF7 was mainly expressed in the nucleus in both normal nasopharyngeal cells and nasopharyngeal cancer cells that expresses LMP1...
July 16, 2017: Pathology International
https://www.readbyqxmd.com/read/28706136/swine-irf3-irf7-attenuates-inflammatory-responses-through-tlr4-signaling-pathway
#10
Pei-Ge Chen, Yan-Jing Guan, Guang-Ming Zha, Xian-Qin Jiao, He-Shui Zhu, Cheng-Yu Zhang, Yue-Ying Wang, He-Ping Li
To explore the role of IRF3/IRF7 during inflammatory responses, we investigated the effects of swine IRF3/IRF7 on TLR4 signaling pathway and inflammatory factors expression in porcine kidney epithelial PK15 cell lines. We successfully constructed eukaryotic vectors PB-IRF3 and PB-IRF7, transfected these vectors into PK15 cells and observed GFP under a fluorescence microscope. In addition, RT-PCR was also used to detect transfection efficiency. We found that IRF3/IRF7 was efficiently overexpressed in PK15 cells...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28698279/zika-virus-persistently-infects-and-is-basolaterally-released-from-primary-human-brain-microvascular-endothelial-cells
#11
Megan C Mladinich, John Schwedes, Erich R Mackow
Zika virus (ZIKV) is a mosquito-borne Flavivirus that has emerged as the cause of encephalitis and fetal microencephaly in the Americas. ZIKV uniquely persists in human bodily fluids for up to 6 months, is sexually transmitted, and traverses the placenta and the blood-brain barrier (BBB) to damage neurons. Cells that support persistent ZIKV replication and mechanisms by which ZIKV establishes persistence remain enigmatic but central to ZIKV entry into protected neuronal compartments. The endothelial cell (EC) lining of capillaries normally constrains transplacental transmission and forms the BBB, which selectively restricts access of blood constituents to neurons...
July 11, 2017: MBio
https://www.readbyqxmd.com/read/28651122/activation-of-irf3-contributes-to-ifn-%C3%AE-and-isg54-expression-during-the-immune-responses-to-b16f10-tumor-growth
#12
Zachary Guinn, Deborah M Brown, Thomas M Petro
Interferon Regulatory Factor (IRF-3) has been shown to contribute to immune control of B16 melanoma tumor growth. We have shown previously that IRF-3 has a role in IFN-γ-induced expression of pro-apoptotic interferon stimulated gene 54 (ISG54) in macrophages and IFN-γ in T cells. To investigate the IRF3-IFN-γ-ISG54 nexus, we injected C57Bl/6 (B6) and IRF3KO mice s.c. with luciferase-producing B16-F10 tumor cells. Tumor growth as measured by luciferase levels was similar between B6 and IRF3KO mice at days 2 and 6, but was significantly greater at day 9 in IRF3KO mice compared with B6 mice...
September 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28634691/modulation-of-rotavirus-severe-gastroenteritis-by-the-combination-of-probiotics-and-prebiotics
#13
REVIEW
Guadalupe Gonzalez-Ochoa, Lilian K Flores-Mendoza, Ramona Icedo-Garcia, Ricardo Gomez-Flores, Patricia Tamez-Guerra
Annual mortality rates due to infectious diarrhea are about 2.2 million; children are the most vulnerable age group to severe gastroenteritis, representing group A rotaviruses as the main cause of disease. One of the main factors of rotavirus pathogenesis is the NSP4 protein, which has been characterized as a viral toxin involved in triggering several cellular responses leading to diarrhea. Furthermore, the rotavirus protein NSP1 has been associated with interferon production inhibition by inducing the degradation of interferon regulatory factors IRF3, IRF5, and IRF7...
June 20, 2017: Archives of Microbiology
https://www.readbyqxmd.com/read/28623344/an-essential-role-of-pi3k-in-the-control-of-west-nile-virus-infection
#14
Leilei Wang, Long Yang, Erol Fikrig, Penghua Wang
The phosphatidyl-inositol-3 kinases (PI3K) pathway regulates a variety of cellular processes, including cell proliferation, RNA processing, protein translation, autophagy, apoptosis and antiviral immunity. Many viruses depend on PI3K signaling for replication. However, its role in flaviviral infection has not been clearly defined. Here we report that PI3K signaling is critical for the control of West Nile virus (WNV) infection by regulating type I IFN (IFN-I) response. Inhibition of PI3K activity by 3-methyl adenine (3-MA), Wortmannin (WM) and LY294002 (LY) increased viral titers by 3-16 folds in primary mouse macrophages, embryonic fibroblasts and human cell lines...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28604814/functional-paralysis-of-gm-csf-derived-bone-marrow-cells-productively-infected-with-ectromelia-virus
#15
Lidia Szulc-Dąbrowska, Justyna Struzik, Agnieszka Ostrowska, Maciej Guzera, Felix N Toka, Magdalena Bossowska-Nowicka, Małgorzata M Gieryńska, Anna Winnicka, Zuzanna Nowak, Marek G Niemiałtowski
Ectromelia virus (ECTV) is an orthopoxvirus responsible for mousepox, a lethal disease of certain strains of mice that is similar to smallpox in humans, caused by variola virus (VARV). ECTV, similar to VARV, exhibits a narrow host range and has co-evolved with its natural host. Consequently, ECTV employs sophisticated and host-specific strategies to control the immune cells that are important for induction of antiviral immune response. In the present study we investigated the influence of ECTV infection on immune functions of murine GM-CSF-derived bone marrow cells (GM-BM), comprised of conventional dendritic cells (cDCs) and macrophages...
2017: PloS One
https://www.readbyqxmd.com/read/28600543/innate-and-adaptive-immunity-are-progressively-activated-in-parallel-with-renal-injury-in-the-5-6-renal-ablation-model
#16
Camilla Fanelli, Simone C A Arias, Flavia G Machado, Jessica K Okuma, Denise M A C Malheiros, Hatylas Azevedo, Carlos A Moreira-Filho, Niels O S Camara, Clarice K Fujihara, Roberto Zatz
The mechanisms triggering renal inflammation in chronic kidney disease (CKD) are unclear. We performed a detailed analysis of the time course of innate and adaptive immunity activation in the 5/6 renal ablation (Nx) model. Munich-Wistar rats undergoing Nx were studied 15, 60 and 120 days after ablation. Hypertension, albuminuria, creatinine retention, interstitial expansion and infiltration by macrophages and T-lymphocytes were already evident 15 days after Nx. PCR-array was used to screen for altered gene expression, whereas gene and protein expressions of TLR4, CASP1, IL-1β and NLRP3 were individually assessed...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28588282/comparison-and-immunobiological-characterization-of-retinoic-acid-inducible-gene-i-like-receptor-expression-in-mesenchymal-stromal-cells
#17
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/28569178/prediction-of-response-to-remission-induction-therapy-by-gene-expression-profiling-of-peripheral-blood-in-japanese-patients-with-microscopic-polyangiitis
#18
Akihiro Ishizu, Utano Tomaru, Sakiko Masuda, Ken-Ei Sada, Koichi Amano, Masayoshi Harigai, Yasushi Kawaguchi, Yoshihiro Arimura, Kunihiro Yamagata, Shoichi Ozaki, Hiroaki Dobashi, Sakae Homma, Yasunori Okada, Hitoshi Sugiyama, Joichi Usui, Naotake Tsuboi, Seiichi Matsuo, Hirofumi Makino
BACKGROUND: Microscopic polyangiitis (MPA), which is classified as an anti-neutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis, is one of the most frequent primary vasculitides in Japan. We earlier nominated 16 genes (IRF7, IFIT1, IFIT5, OASL, CLC, GBP-1, PSMB9, HERC5, CCR1, CD36, MS4A4A, BIRC4BP, PLSCR1, DEFA1/DEFA3, DEFA4, and COL9A2) as predictors of response to remission induction therapy against MPA. The aim of this study is to determine the accuracy of prediction using these 16 predictors...
May 31, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28569041/predictive-value-of-tlr7-polymorphism-for-cetuximab-based-chemotherapy-in-patients-with-metastatic-colorectal-cancer
#19
Satoshi Okazaki, Sebastian Stintzing, Yu Sunakawa, Shu Cao, Wu Zhang, Dongyun Yang, Yan Ning, Satoshi Matsusaka, Martin D Berger, Yuji Miyamoto, Mitsukuni Suenaga, Marta Schirripa, Jordan D West, Roel Gopez, Tsuji Akihito, Wataru Ichikawa, Volker Heinemann, R William DePaolo, Heinz-Josef Lenz
The TLR7 and TLR9 signalings are implicated in the regulation of the immune system through type-I interferon induction. Preclinical studies have demonstrated the immunomodulatory and antitumor effects of TLR7 and TLR9 agonists in combination with cetuximab. We tested the hypothesis that genetic variations in TLR7 and TLR9 and their downstream molecules IRF5 and IRF7 were associated with outcomes in metastatic colorectal cancer (mCRC) patients receiving cetuximab-based chemotherapy. Six single nucleotide polymorphisms (SNPs) in TLR7, TLR9, IRF5 and IRF7 were tested for the association with RR, PFS, and OS in KRAS-wild type mCRC patients...
September 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28560754/oncostatin-m-induces-rig-i-and-mda5-expression-and-enhances-the-double-stranded-rna-response-in-fibroblasts
#20
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
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