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https://www.readbyqxmd.com/read/28087227/a-novel-kindred-with-inherited-stat2-deficiency-and-severe-viral-illness
#1
Leen Moens, Lien Van Eyck, Dirk Jochmans, Tania Mitera, Glynis Frans, Xavier Bossuyt, Patrick Matthys, Johan Neyts, Michael Ciancanelli, Shen-Ying Zhang, Rik Gijsbers, Jean-Laurent Casanova, Stephanie Boisson-Dupuis, Isabelle Meyts, Adrian Liston
No abstract text is available yet for this article.
January 5, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28069291/antagonizing-cytokine-mediated-jak-stat-signaling-by-porcine-reproductive-and-respiratory-syndrome-virus
#2
REVIEW
Liping Yang, Yan-Jin Zhang
Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway is activated by myriad cytokines, which are involved in regulation of cell growth, proliferation, differentiation, apoptosis, angiogenesis, immunity and inflammatory response. Because of its significance in immune response, JAK-STAT pathway is often targeted by pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV causes reproductive failure in sows and respiratory disease in pigs of all ages...
December 30, 2016: Veterinary Microbiology
https://www.readbyqxmd.com/read/28062696/prostaglandin-e2-inhibition-of-il-27-production-in-murine-dendritic-cells-a-novel-mechanism-that-involves-irf1
#3
Kirsten M Hooper, Jui-Hung Yen, Weimin Kong, Kate M Rahbari, Ping-Chang Kuo, Ana M Gamero, Doina Ganea
IL-27, a multifunctional cytokine produced by APCs, antagonizes inflammation by affecting conventional dendritic cells (cDC), inducing IL-10, and promoting development of regulatory Tr1 cells. Although the mechanisms involved in IL-27 induction are well studied, much less is known about the factors that negatively impact IL-27 expression. PGE2, a major immunomodulatory prostanoid, acts as a proinflammatory agent in several models of inflammatory/autoimmune disease, promoting primarily Th17 development and function...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28003963/transcriptome-analysis-reveals-common-differential-and-global-gene-expression-profiles-in-bluetongue-virus-serotype-16-btv-16-infected-peripheral-blood-mononuclear-cells-pbmcs-in-sheep-and-goats
#4
Anjali Singh, Minakshi Prasad, Bina Mishra, Siddappa Manjunath, Amit Ranjan Sahu, G Bhuvana Priya, Sajad Ahmad Wani, Aditya Prasad Sahoo, Amit Kumar, Shweta Balodi, Anupama Deora, Shikha Saxena, Ravi Kumar Gandham
Bluetongue is an economically important infectious, arthropod borne viral disease of domestic and wild ruminants, caused by Bluetongue virus (BTV). Sheep are considered the most susceptible hosts, while cattle, buffalo and goats serve as reservoirs. The viral pathogenesis of BTV resulting in presence or absence of clinical disease among different hosts is not clearly understood. In the present study, transcriptome of sheep and goats peripheral blood mononuclear cells infected with BTV-16 was explored. The differentially expressed genes (DEGs) identified were found to be significantly enriched for immune system processes - NFκB signaling, MAPK signaling, Ras signaling, NOD signaling, RIG signaling, TNF signaling, TLR signaling, JAK-STAT signaling and VEGF signaling pathways...
March 2017: Genomics Data
https://www.readbyqxmd.com/read/28003146/injectable-hyaluronic-acid-down-regulates-interferon-signaling-molecules-igfbp3-and-ifit3-in-the-bovine-intervertebral-disc
#5
Zepur Kazezian, Zhen Li, Mauro Alini, Sibylle Grad, Abhay Pandit
: Low back pain which is a major cause of disability for people aged between 20 and 50 years imposes a serious socio-economic burden. The current focus of regenerative medicine is on identifying molecular markers to facilitate the design of targeted therapeutics. Previously, we have demonstrated that expression of the anti-proliferative interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) and pro-apoptotic insulin-like growth factor-binding protein-3 (IGFBP3), are up-regulated as downstream targets of the inflammatory cytokine interferon α (IFNα) signaling pathway in the human annulus fibrosus (AF)...
December 18, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27988795/a-novel-anti-viral-role-for-stat3-in-ifn-%C3%AE-signalling-responses
#6
Rebecca Mahony, Siobhán Gargan, Kim L Roberts, Nollaig Bourke, Sinead E Keating, Andrew G Bowie, Cliona O'Farrelly, Nigel J Stevenson
The cytokine, Interferon (IFN)-α, induces a wide spectrum of anti-viral mediators, via the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. STAT1 and STAT2 are well characterised to upregulate IFN-stimulated gene (ISG) expression; but even though STAT3 is also activated by IFN-α, its role in anti-viral ISG induction is unclear. Several viruses, including Hepatitis C and Mumps, reduce cellular STAT3 protein levels, via the promotion of ubiquitin-mediated proteasomal degradation...
December 17, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27929099/stat1-is-essential-for-the-inhibition-of-hepatitis-c-virus-replication-by-interferon-%C3%AE-but-not-by-interferon-%C3%AE
#7
Shota Yamauchi, Kenji Takeuchi, Kazuyasu Chihara, Chisato Honjoh, Yuji Kato, Hatsumi Yoshiki, Hak Hotta, Kiyonao Sada
Interferon-α (IFN-α) and IFN-λ are structurally distinct cytokines that bind to different receptors, but induce expression of similar sets of genes through Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathways. The difference between IFN-α and IFN-λ signaling remains poorly understood. Here, using the CRISPR/Cas9 system, we examine the role of STAT1 and STAT2 in the inhibition of hepatitis C virus (HCV) replication by IFN-α and IFN-λ. Treatment with IFN-α increases expression of IFN-stimulated genes (ISGs) such as double-stranded RNA-activated protein kinase (PKR) and decreases viral RNA and protein levels in HCV-infected Huh-7...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910206/balance-between-il-3-and-type-iinterferons-and-their-interrelationship-with-fasl-dictates-lifespan-and-effector-functions-of-human-basophils
#8
B R Hagmann, A Odermatt, T Kaufmann, C A Dahinden, M Fux
BACKGROUND: In contrast to eosinophils and neutrophils, the regulation of the lifespan of human basophils is poorly defined, with the exception of the potent anti-apoptotic effect of IL-3 that also promotes pro-inflammatory effector functions and phenotypic changes. Type I IFNs (IFN-α, IFN-β), which are well known for their anti-viral activities, have the capacity to inhibit allergic inflammation. OBJECTIVE: To elucidate whether type I IFNs have the potential to abrogate the lifespan and/or effector functions of human basophils...
January 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27907166/vaccinia-virus-protein-c6-inhibits-type-i-ifn-signalling-in-the-nucleus-and-binds-to-the-transactivation-domain-of-stat2
#9
Jennifer H Stuart, Rebecca P Sumner, Yongxu Lu, Joseph S Snowden, Geoffrey L Smith
The type I interferon (IFN) response is a crucial innate immune signalling pathway required for defense against viral infection. Accordingly, the great majority of mammalian viruses possess means to inhibit this important host immune response. Here we show that vaccinia virus (VACV) strain Western Reserve protein C6, is a dual function protein that inhibits the cellular response to type I IFNs in addition to its published function as an inhibitor of IRF-3 activation, thereby restricting type I IFN production from infected cells...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27881648/modeling-severe-fever-with-thrombocytopenia-syndrome-virus-infection-in-golden-syrian-hamsters-importance-of-stat2-in-preventing-disease-and-effective-treatment-with-favipiravir
#10
Brian B Gowen, Jonna B Westover, Jinxin Miao, Arnaud J Van Wettere, Johanna D Rigas, Brady T Hickerson, Kie-Hoon Jung, Rong Li, Bettina L Conrad, Skot Nielson, Yousuke Furuta, Zhongde Wang
: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease endemic in parts of Asia. The etiologic agent, SFTS virus (SFTSV; family Bunyaviridae, genus Phlebovirus) has caused significant morbidity and mortality in China, South Korea, and Japan, with key features of disease being intense fever, thrombocytopenia, and leukopenia. Case fatality rates are estimated to be in the 30% range, and no antivirals or vaccines are approved for use for treatment and prevention of SFTS...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27855377/inhibition-of-stat-pathway-impairs-anti-hepatitis-c-virus-effect-of-interferon-alpha
#11
Lan-Juan Zhao, Sheng-Fei He, Yuan Liu, Ping Zhao, Zhong-Qi Bian, Zhong-Tian Qi
BACKGROUND/AIMS: Signal transducer and activator of transcription (STAT) pathway plays an important role in antiviral efficacy of interferon alpha (IFN-α). IFN-α is the main therapeutic against hepatitis C virus (HCV) infection. We explored effects of IFN-α on HCV replication and antiviral gene expression by targeting STAT. METHODS: In response to IFN-α, STAT status, HCV replication, and antiviral gene expression were analyzed in human hepatoma Huh7.5.1 cells before and after cell culture-derived HCV infection...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27852626/negative-regulation-of-type-i-ifn-signaling-by-phosphorylation-of-stat2-on-t387
#12
Yuxin Wang, Jing Nan, Belinda Willard, Xin Wang, Jinbo Yang, George R Stark
The transcription factor ISGF3, comprised of IRF9 and tyrosine-phosphorylated STATs 1 and 2, transmits the signal from the type I interferon receptor to the genome. We have discovered a novel phosphorylation of STAT2 on T387 that negatively regulates this response. In most untreated cell types, the majority of STAT2 is phosphorylated on T387 constitutively. In response to interferon-β, the T387A mutant of STAT2 is much more effective than wild-type STAT2 in mediating the expression of many interferon-stimulated genes, in protecting cells against virus infection, and in inhibiting cell growth...
January 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/27836955/ifn-%C3%AE-ifn-%C3%AE-responses-to-respiratory-viruses-in-paediatric-asthma
#13
Annika Bergauer, Nina Sopel, Bettina Kroß, Tytti Vuorinen, Paraskevi Xepapadaki, Scott T Weiss, Ashley Blau, Himanshu Sharma, Cornelia Kraus, Rebekka Springel, Manfred Rauh, Susanne Mittler, Anna Graser, Theodor Zimmermann, Volker O Melichar, Alexander Kiefer, Marek L Kowalski, Anna Sobanska, Tuomas Jartti, Heikki Lukkarinen, Nikolaos G Papadopoulos, Susetta Finotto
We analysed the influence of rhinovirus (RV) in nasopharyngeal fluid (NPF) on type I and III interferon (IFN) responses (e.g. IFN-α and IFN -: λ) and their signal transduction, at baseline and during disease exacerbation, in cohorts of pre-school children with and without asthma.At the time of recruitment into the Europe-wide study PreDicta, and during symptoms, NPF was collected and the local RV colonisation was analysed. Peripheral blood mononuclear cells (PBMCs) were challenged in vitro with RV or not...
November 11, 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/27825821/constitutive-overexpressed-type-i-interferon-induced-downregulation-of-antiviral-activity-in-medaka-fish-oryzias-latipes
#14
Shun Maekawa, Takashi Aoki, Han-Ching Wang
In fish, as well as vertebrates, type I interferons (IFNs) are important cytokines that help to provide innate, antiviral immunity. Although low amounts of IFN are constitutively secreted under normal physiological conditions, long-term and excessive IFN stimulation leads to reduced sensitivity to the IFN signal. This provides a negative feedback mechanism that prevents inappropriate responses and autoimmunity. At present, however, neither IFN desensitization nor the normal physiological role of constitutive IFN are well characterized in fish...
March 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/27803128/stat-mutations-as-program-switchers-turning-primary-immunodeficiencies-into-autoimmune-diseases
#15
REVIEW
Tiziana Lorenzini, Laura Dotta, Mauro Giacomelli, Donatella Vairo, Raffaele Badolato
STAT proteins are a family of transcription factors that mediate cellular response to cytokines and growth factors. Study of patients with familial susceptibility to pathogens and/or autoimmune diseases has led to the identification of 7 inherited disorders that are caused by mutations of 4 STAT family genes. Homozygous or compound heterozygous mutations of STAT1 lead to complete or partial forms of STAT1 deficiency that are associated with susceptibility to intracellular pathogens and herpetic infections. Patients with heterozygous STAT1 gain-of-function (GOF) mutations usually present with chronic mucocutaneous candidiasis (CMC) but may also experience bacterial and viral infections, autoimmune manifestations, lymphopenia, cerebral aneurysms, and increased risk to develop tumors...
January 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27802159/phosphorylation-of-stat2-on-serine-734-negatively-regulates-the-ifn-%C3%AE-induced-antiviral-response
#16
Håkan C Steen, Kevin P Kotredes, Shoko Nogusa, Michele Y Harris, Siddharth Balachandran, Ana M Gamero
Serine phosphorylation of STAT proteins is an important post-translational modification event that, in addition to tyrosine phosphorylation, is required for strong transcriptional activity. However, we recently showed that phosphorylation of STAT2 on S287 induced by type I interferons (IFN-α and IFN-β), evoked the opposite effect. S287-STAT2 phosphorylation inhibited the biological effects of IFN-α. We now report the identification and characterization of S734 on the C-terminal transactivation domain of STAT2 as a new phosphorylation site that can be induced by type I IFNs...
November 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27797853/zika-virus-inhibits-type-i-interferon-production-and-downstream-signaling
#17
Anil Kumar, Shangmei Hou, Adriana M Airo, Daniel Limonta, Valeria Mancinelli, William Branton, Christopher Power, Tom C Hobman
Zika virus is an emerging mosquito-borne pathogen that is associated with Guillain-Barré syndrome in adults and microcephaly and other neurological defects in newborns. Despite being declared an international emergency by the World Health Organization, comparatively little is known about its biology. Here, we investigate the strategies employed by the virus to suppress the host antiviral response. We observe that once established, Zika virus infection is impervious to interferon treatment suggesting that the virus deploys effective countermeasures to host cell defences...
December 2016: EMBO Reports
https://www.readbyqxmd.com/read/27782195/global-functional-profiling-of-human-ubiquitome-identifies-e3-ubiquitin-ligase-dcst1-as-a-novel-negative-regulator-of-type-i-interferon-signaling
#18
Sajith Nair, Pradeep Bist, Neha Dikshit, Manoj N Krishnan
Type I interferon (IFN-I) mediated innate immune response controls virus infections by inducing the expression of interferon stimulated genes (ISGs). Although ubiquitination plays key roles in immune signaling regulation, a human genome-wide understanding of the role of E3 ubiquitin ligases in interferon mediated ISG induction is lacking. Here, we report a genome-wide profiling of the effect of ectopic expression of 521 E3 ubiquitin ligases and substrate recognition subunits encoded in the human genome (which constitutes 84...
October 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27780205/stat2-is-a-pervasive-cytokine-regulator-due-to-its-inhibition-of-stat1-in-multiple-signaling-pathways
#19
Johnathan Ho, Christin Pelzel, Andreas Begitt, Maureen Mee, Hany M Elsheikha, David J Scott, Uwe Vinkemeier
STAT2 is the quintessential transcription factor for type 1 interferons (IFNs), where it functions as a heterodimer with STAT1. However, the human and murine STAT2-deficient phenotypes suggest important additional and currently unidentified type 1 IFN-independent activities. Here, we show that STAT2 constitutively bound to STAT1, but not STAT3, via a conserved interface. While this interaction was irrelevant for type 1 interferon signaling and STAT1 activation, it precluded the nuclear translocation specifically of STAT1 in response to IFN-γ, interleukin-6 (IL-6), and IL-27...
October 2016: PLoS Biology
https://www.readbyqxmd.com/read/27640307/recurrent-de-novo-and-biallelic-variation-of-atad3a-encoding-a-mitochondrial-membrane-protein-results-in-distinct-neurological-syndromes
#20
Tamar Harel, Wan Hee Yoon, Caterina Garone, Shen Gu, Zeynep Coban-Akdemir, Mohammad K Eldomery, Jennifer E Posey, Shalini N Jhangiani, Jill A Rosenfeld, Megan T Cho, Stephanie Fox, Marjorie Withers, Stephanie M Brooks, Theodore Chiang, Lita Duraine, Serkan Erdin, Bo Yuan, Yunru Shao, Elie Moussallem, Costanza Lamperti, Maria A Donati, Joshua D Smith, Heather M McLaughlin, Christine M Eng, Magdalena Walkiewicz, Fan Xia, Tommaso Pippucci, Pamela Magini, Marco Seri, Massimo Zeviani, Michio Hirano, Jill V Hunter, Myriam Srour, Stefano Zanigni, Richard Alan Lewis, Donna M Muzny, Timothy E Lotze, Eric Boerwinkle, Richard A Gibbs, Scott E Hickey, Brett H Graham, Yaping Yang, Daniela Buhas, Donna M Martin, Lorraine Potocki, Claudio Graziano, Hugo J Bellen, James R Lupski
ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded mitochondrial membrane protein implicated in mitochondrial dynamics, nucleoid organization, protein translation, cell growth, and cholesterol metabolism. We identified a recurrent de novo ATAD3A c.1582C>T (p.Arg528Trp) variant by whole-exome sequencing (WES) in five unrelated individuals with a core phenotype of global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy. We also describe two families with biallelic variants in ATAD3A, including a homozygous variant in two siblings, and biallelic ATAD3A deletions mediated by nonallelic homologous recombination (NAHR) between ATAD3A and gene family members ATAD3B and ATAD3C...
October 6, 2016: American Journal of Human Genetics
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