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type I interferon

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https://www.readbyqxmd.com/read/29161701/yin-yang-1-dynamically-regulates-antiviral-innate-immune-responses-during-viral-infection
#1
Jie Zan, Hao Zhang, Ai-Ping Gu, Kai-Lun Zhong, Min-Yi Lu, Xiao-Xin Bai, Jin-Yang Zhang, Jun Cai
BACKGROUND/AIMS: Type I interferon (IFN-1) production and IFN-1 signaling play critical roles in the host antiviral innate immune responses. Although transcription factor Yin Yang 1 (YY1) has been reported to have a dual activator/repressor role during the regulation of interferon beta (IFN-β) promoter activity, the roles of YY1 in the regulation of upstream signaling pathways leading to IFN-1 induction and IFN-1 signaling during viral infection remain to be elucidated. METHODS: The roles of YY1 in IFN-1 production and IFN-1 signaling were investigated using immunoblotting, real-time PCR, small interfering RNA (siRNA)-mediated YY1 knockdown, YY1 overexpression by transient transfection, and co-immunoprecipitation, using mouse cells...
November 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29161093/b-cells-producing-type-i-interferon-modulate-macrophage-polarization-in-tuberculosis
#2
Alan Bénard, Imme Sakwa, Pablo Schierloh, André Colom, Ingrid Mercier, Ludovic Tailleux, Luc Jouneau, Pierre Boudinot, Talal Al-Saati, Roland Lang, Jan Rehwinkel, Andre G Loxton, Stefan He Kaufmann, Véronique Anton-Leberre, Anne O'Garra, Maria Del Carmen Sasiain, Brigitte Gicquel, Simon Fillatreau, Olivier Neyrolles, Denis Hudrisier
RATIONALE: In addition to their well-known function as antibody-producing cells, B lymphocytes can markedly influence the course of infectious or non-infectious diseases via antibody-independent mechanisms. In tuberculosis, B cells accumulate in lungs, yet their functional contribution to the host response remains poorly understood. OBJECTIVES: To document the role of B cells in tuberculosis in an unbiased manner. METHODS: We generated the transcriptome of B cells isolated from Mycobacterium tuberculosis (Mtb)-infected mice, and validated the identified key pathways using in vitro and in vivo assays...
November 21, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29159280/insertion-of-the-type-i-ifn-decoy-receptor-b18r-in-a-mirna-tagged-semliki-forest-virus-improves-oncolytic-capacity-but-results-in-neurotoxicity
#3
Tina Sarén, Mohanraj Ramachandran, Miika Martikainen, Di Yu
Oncolytic Semliki Forest virus (SFV) has been suggested as a potential candidate for the treatment of glioblastoma and neuroblastoma. However, the oncolytic capacity of SFV is restricted by the anti-viral type-I interferon (IFN) response. The aim of this study was to increase the oncolytic capacity of a microRNA target tagged SFV against glioblastoma by arming it with the Vaccinia-virus-encoded type-I IFN decoy receptor B18R (SFV4B18RmiRT) to neutralize type-I IFN response. Expression of B18R by SFV4B18RmiRT aided neutralization of IFN-β, which was shown by reduced STAT-1 phosphorylation and improved virus spread in plaque assays...
December 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29158604/antiviral-cd8-t-cells-induce-zika-virus-associated-paralysis-in-mice
#4
Kellie A Jurado, Laura J Yockey, Patrick W Wong, Sarah Lee, Anita J Huttner, Akiko Iwasaki
Zika virus (ZIKV) is an emerging, mosquito-borne RNA virus. The rapid spread of ZIKV within the Americas has unveiled microcephaly (1) and Guillain-Barré syndrome (2,3) as ZIKV-associated neurological complications. Recent reports have also indicated other neurological manifestations to be associated with ZIKV, including myelitis (4) , meningoencephalitis (5) and fatal encephalitis (6) . Here, we investigate the neuropathogenesis of ZIKV infection in type I interferon receptor IFNAR knockout (Ifnar1 (-/-) ) mice, an infection model that exhibits high viral burden within the central nervous system...
November 20, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/29157967/the-role-of-interferon-in-persistent-viral-infection-insights-from-murine-norovirus
#5
REVIEW
Timothy J Nice, Bridget A Robinson, Jacob A Van Winkle
Persistent viral infections result from evasion or avoidance of sterilizing immunity, extend the timeframe of virus transmission, and can trigger disease. Prior studies in mouse models of persistent infection have suggested that ineffective adaptive immune responses are necessary for persistent viral infection. However, recent work in the murine norovirus (MNV) model of persistent infection demonstrates that innate immunity can control both early and persistent viral replication independently of adaptive immune effector functions...
November 17, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/29156530/microrna-373-facilitates-hsv-1-replication-through-suppression-of-type-i-ifn-response-by-targeting-irf1
#6
Yiting Xie, Songlin He, Jinhua Wang
Herpes simplex virus type 1 (HSV-1) had led to kinds of clinical disorders and became an important cause of morbidity and mortality worldwide, such as herpetic gingivostomatitis in children. Previous studies reported that HSV-1 infection is common and has evolved a variety of mechanisms to evade the immune system, such as dysregulation of miRNAs. However, reports concerning the role of miRNA in HSV-1infection are limited. Here, we report that a host microRNA, miR-373, was significantly upregulated by HSV-1 infection in Hela cells and patients with herpetic gingivostomatitis and it facilitated HSV-1 replication in vitro...
November 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29156047/immunopathogenesis-of-hepatitis-b-virus
#7
Tai-Chung Tseng, Li-Rung Huang
Chronic hepatitis B virus (HBV) infection is a global public health issue. There are >250 million people chronically infected with HBV, and these chronic carriers are at high risk of developing end-stage liver diseases and hepatocellular carcinoma. Patients with chronic hepatitis B (CHB) usually acquire the virus perinatally, while most patients infected during adulthood develop acute hepatitis B (AHB), which usually results in viral clearance. HBV infection is noncytopathic, and liver injury is mostly contributed by host immune responses...
November 16, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29155197/dyrk2-mediated-the-release-of-proinflammatory-cytokines-in-lps-induced-bv2-cells
#8
Li Xu, Yuxiang Sun, Mengmeng Li, Xin Ge
NF-κB pathway and p38MAPK (p38mitogen-activated protein kinase) pathway have been shown to play a key role in neuroinflammation, however, the phosphorylation modification is an important process that affects the activation of above pathways. Dual-specificity tyrosine-phosphorylation-regulated kinase 2(Dyrk2), as a phosphokinase that can phosphorylate signal molecules, has been demonstrated to regulate Type I Interferon(TIF) by promoting ser527 phosphorylation of TBK1. Therefore, to investigate the role of Dyrk2 in neuroinflammation, we analyzed the effect of Dyrk2 on LPS-induced the activation of microglia...
November 16, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29155101/type-i-ifn-related-netosis-in-ataxia-telangiectasia-and-artemis-deficiency
#9
Ersin Gul, Esra Hazar Sayar, Bilgi Gungor, Fehime Kara Eroglu, Naz Surucu, Sevgi Keles, Sukru Nail Guner, Sıddıka Fındık, Esin Alpdündar, Ihsan Cihan Ayanoglu, Basak Kayaoglu, Busra Nur Geçkin, Hatice Asena Sanli, Tamer Kahraman, Cengiz Yakicier, Meltem Muftuoglu, Berna Oguz, Deniz Nazire Cagdas Ayvaz, Ihsan Gursel, Seza Ozen, Ismail Reisli, Mayda Gursel
BACKGROUND: Pathological inflammatory syndromes of unknown etiology are commonly observed in Ataxia telangiectasia (AT) and Artemis deficiency. Similar inflammatory manifestations also exist in STING-associated vasculopathy in infancy (SAVI) patients. OBJECTIVE: To test the hypothesis that the inflammation associated manifestations observed in AT and Artemis deficient patients stem from increased type I IFN signature leading to neutrophil mediated pathological damage...
November 15, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29152879/y-rna-derived-small-rnas-in-sj%C3%A3-gren-s-syndrome-candidate-biomarkers
#10
Jayakanthan Kabeerdoss, Pulukool Sandhya, Debashish Danda
Anti-Ro and anti-La antibodies are important in pathogenesis and diagnosis of Sjögren's syndrome (SS). Ro60, Ro52 and La are RNA binding proteins of Y RNA, which were discovered more than three decades ago. Significance of Y RNA is not appreciated as much as Ro and La in SS. It can be hypothesised that 5'-YsRNA, short fragment derived from Y RNA may be recognized by TLR7 in pDC, which induces type I interferon signature in SS. New genomics tools, namely RNA seq, enables assay of 5'-YsRNA in blood. 5'-YsRNA has the potential to be a novel biomarker of SS...
November 19, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/29152578/middle-east-respiratory-syndrome-coronavirus-nonstructural-protein-16-is-necessary-for-interferon-resistance-and-viral-pathogenesis
#11
Vineet D Menachery, Lisa E Gralinski, Hugh D Mitchell, Kenneth H Dinnon, Sarah R Leist, Boyd L Yount, Rachel L Graham, Eileen T McAnarney, Kelly G Stratton, Adam S Cockrell, Kari Debbink, Amy C Sims, Katrina M Waters, Ralph S Baric
Coronaviruses (CoVs) encode a mixture of highly conserved and novel genes, as well as genetic elements necessary for infection and pathogenesis, raising the possibility of common targets for attenuation and therapeutic design. In this study, we focused on highly conserved nonstructural protein 16 (NSP16), a viral 2'O-methyltransferase (2'O-MTase) that encodes critical functions in immune modulation and infection. Using reverse genetics, we disrupted a key motif in the conserved KDKE motif of Middle East respiratory syndrome CoV (MERS-CoV) NSP16 (D130A) and evaluated the effect on viral infection and pathogenesis...
November 2017: MSphere
https://www.readbyqxmd.com/read/29150602/tlr7-mediated-viral-recognition-results-in-focal-type-i-interferon-secretion-by-dendritic-cells
#12
Shin-Ichiroh Saitoh, Fumiko Abe, Atsuo Kanno, Natsuko Tanimura, Yoshiko Mori Saitoh, Ryutaro Fukui, Takuma Shibata, Katsuaki Sato, Takeshi Ichinohe, Mayumi Hayashi, Kazuishi Kubota, Hiroko Kozuka-Hata, Masaaki Oyama, Yorifumi Kikko, Toshiaki Katada, Kenji Kontani, Kensuke Miyake
Plasmacytoid dendritic cells (pDC) sense viral RNA through toll-like receptor 7 (TLR7), form self-adhesive pDC-pDC clusters, and produce type I interferons. This cell adhesion enhances type I interferon production, but little is known about the underlying mechanisms. Here we show that MyD88-dependent TLR7 signaling activates CD11a/CD18 integrin to induce microtubule elongation. TLR7(+) lysosomes then become linked with these microtubules through the GTPase Arl8b and its effector SKIP/Plekhm2, resulting in perinuclear to peripheral relocalization of TLR7...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29150432/the-ikk-related-kinase-tbk1-activates-mtorc1-directly-in-response-to-growth-factors-and-innate-immune-agonists
#13
Cagri Bodur, Dubek Kazyken, Kezhen Huang, Bilgen Ekim Ustunel, Kate A Siroky, Aaron Seth Tooley, Ian E Gonzalez, Daniel H Foley, Hugo A Acosta-Jaquez, Tammy M Barnes, Gabrielle K Steinl, Kae-Won Cho, Carey N Lumeng, Steven M Riddle, Martin G Myers, Diane C Fingar
The innate immune kinase TBK1 initiates inflammatory responses to combat infectious pathogens by driving production of type I interferons. TBK1 also controls metabolic processes and promotes oncogene-induced cell proliferation and survival. Here, we demonstrate that TBK1 activates mTOR complex 1 (mTORC1) directly. In cultured cells, TBK1 associates with and activates mTORC1 through site-specific mTOR phosphorylation (on S2159) in response to certain growth factor receptors (i.e., EGF-receptor but not insulin receptor) and pathogen recognition receptors (PRRs) (i...
November 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29150429/cgamp-a-tale-of-two-signals
#14
Teneema Kuriakose, Thirumala-Devi Kanneganti
In this issue of JEM, Swanson et al. (https://doi.org/10.1084/jem.20171749) report an unanticipated role for cGAMP in priming and activation of inflammasomes in addition to its well-characterized function as an endogenous second messenger inducing type I interferons in the cytosolic DNA-sensing pathway.
November 17, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29150375/type-i-interferon-and-proinflammatory-cytokine-levels-in-cerebrospinal-fluid-of-newborns-with-rotavirus-associated-leukoencephalopathy
#15
Kyung Yeon Lee, Chang Hoon Moon, Seong Hoon Choi
OBJECTIVE: The purpose of this study was to identify whether there is an increase in type I interferon and proinflammatory cytokine levels in the cerebrospinal fluid of newborns with rotavirus-associated leukoencephalopathy. METHODS: Levels of type I interferons (interferon-alpha and interferon-beta) and proinflammatory cytokines (interleukin-6 and interferon-gamma) were measured in the cerebrospinal fluid of 23 newborns with rotavirus-associated leukoencephalopathy (patient group) and 39 infants under 90 days-of-age (control group)...
November 14, 2017: Brain & Development
https://www.readbyqxmd.com/read/29150240/dichotomous-expression-of-tnf-superfamily-ligands-on-antigen-presenting-cells-controls-post-priming-anti-viral-cd4-t-cell-immunity
#16
Yu-Han Chang, Kuan Chung Wang, Kuan-Lun Chu, Derek L Clouthier, Anh T Tran, Miguel S Torres Perez, Angela C Zhou, Ali A Abdul-Sater, Tania H Watts
T cell antigen-presenting cell (APC) interactions early during chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITR is important for CD4(+) T cell accumulation and control of chronic lymphocytic choriomeningitis virus (LCMV). We found that type I interferon (IFN-I) induced TNFSF ligands GITRL, 4-1BBL, OX40L, and CD70 predominantly on monocyte-derived APCs and CD80 and CD86 predominantly on classical dendritic cells (cDCs)...
November 13, 2017: Immunity
https://www.readbyqxmd.com/read/29146236/infectious-bursal-disease-virus-protein-vp4-suppresses-type-i-interferon-expression-via-inhibiting-k48-linked-ubiquitylation-of-glucocorticoid-induced-leucine-zipper-gilz
#17
Zhiyuan He, Xiang Chen, Mengjiao Fu, Jun Tang, Xiaoqi Li, Hong Cao, Yongqiang Wang, Shijun J Zheng
Viruses have developed a variety of methods to evade host immune response. Our previous study showed that infectious bursal disease virus (IBDV) inhibited type I interferon production via interaction of VP4 with cellular glucocorticoid-induced leucine zipper (GILZ) protein. However, the exact underlying molecular mechanism is still unclear. In this study, we found that IBDV VP4 suppressed GILZ degradation by inhibiting K48-linked ubiquitylation of GILZ. Furthermore, mutation of VP4 (R41G) abolished the inhibitory effect of VP4 on IFN-β expression and GILZ ubiquitylation, indicating that the amino acid 41R of VP4 was required for the suppression of IFN-β expression and GILZ ubiquitylation...
October 28, 2017: Immunobiology
https://www.readbyqxmd.com/read/29146054/lymphocytic-thrombophilic-arteritis-a-distinct-inflammatory-type-i-interferon-and-c5b-9-mediated-subcutaneous-endovasculitis
#18
Cynthia M Magro, Jad Saab
BACKGROUND: Lymphocytic thrombophilic arteritis is a recently recognized subcuticular larger vessel vasculitis characterized by striking vascular luminal thrombosis. METHODS: The clinical features, histopathology and phenotypic profile of ten patients with lymphocytic thrombophilic arteritis were explored in an attempt to better define the entity from a clinical and pathophysiologic perspective. RESULTS: The patients were all female (mean age of 43) presenting with generally asymptomatic lower and upper extremity hyperpigmented macules...
December 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29145159/potential-link-between-m-6-a-modification-and-systemic-lupus-erythematosus
#19
REVIEW
Lian-Ju Li, Yin-Guang Fan, Rui-Xue Leng, Hai-Feng Pan, Dong-Qing Ye
The field of m(6)A modification and epitranscriptomics has recently attracted much attention. More methods allowing for precise m(6)A site profiling and location are developed and crucial players of m(6)A modification machinery are increasingly identified. Although some challenges remain, m(6)A modification is found to modulate almost all aspects of RNA metabolism, such as splicing, stability, structure, translation, and export. Thus, m(6)A modification adds a new layer of post-transcriptional gene expression regulation, and it is implicated in T cell response to HIV infection, type I interferon production, and T cell differentiation and homeostasis...
November 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29136142/the-forkhead-transcription-factor-foxo3-negatively-regulates-natural-killer-cell-function-and-viral-clearance-in-myocarditis
#20
Madlen Loebel, Luise Holzhauser, Jelka A Hartwig, Praphulla C Shukla, Konstantinos Savvatis, Alexander Jenke, Martina Gast, Felicitas Escher, Sonya C Becker, Sandra Bauer, Andrea Stroux, Antje Beling, Meike Kespohl, Sandra Pinkert, Henry Fechner, Uwe Kuehl, Dirk Lassner, Wolfgang Poller, Heinz-Peter Schultheiss, Tanja Zeller, Stefan Blankenberg, Anna-Pia Papageorgiou, Stephane Heymans, Ulf Landmesser, Carmen Scheibenbogen, Carsten Skurk
Aims: Foxo3 is a transcription factor involved in cell metabolism, survival, and inflammatory disease. However, mechanistic insight in Foxo3 effects is still limited. Here, we investigated the role of Foxo3 on natural killer (NK) cell responses and its effects in viral myocarditis. Methods and results: Effects of Foxo3 on viral load and immune responses were investigated in a model of coxsackie virus B3 myocarditis in wild-type (WT) and Foxo3 deficient mice. Reduced immune cell infiltration, viral titres, and pro-inflammatory cytokines in cardiac tissue were observed in Foxo3-/- mice 7 days post-infection (p...
November 9, 2017: European Heart Journal
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