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type 1 interferon

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https://www.readbyqxmd.com/read/29782060/autosomal-dominant-early-onset-spastic-paraparesis-with-brain-calcification-due-to-ifih1-gain-of-function
#1
Lyse Ruaud, Gillian I Rice, Christelle Cabrol, Juliette Piard, Mathieu Rodero, Lien van Eyk, Elise Boucher-Brischoux, Alain Maertens de Noordhout, Ricardo Maré, Emmanuel Scalais, Fernand Pauly, François-Guillaume Debray, William Dobyns, Carolina Uggenti, Ji Woo Park, Sun Hur, John H Livingston, Yanick J Crow, Lionel Van Maldergem
We describe progressive spastic paraparesis in two male siblings and the daughter of one of these individuals. Onset of disease occurred within the first decade, with stiffness and gait difficulties. Brisk deep tendon reflexes and extensor plantar responses were present, in the absence of intellectual disability or dermatological manifestations. Cerebral imaging identified intracranial calcification in all symptomatic family members. A marked upregulation of interferon stimulated gene (ISG) transcripts was recorded in all three affected individuals and in two clinically unaffected relatives...
May 21, 2018: Human Mutation
https://www.readbyqxmd.com/read/29775750/the-effects-of-capn1-gene-inactivation-on-the-differential-expression-of-genes-in-skeletal-muscle
#2
William T Olive, Brittney N Keel, Amanda K Lindholm-Perry, Justyna Horodyska, Andrew P Foote
Protein turnover is required for muscle growth and regeneration and several proteolytic enzymes, including the calpains, degrade myofibrillar proteins during this process. In a previous experiment, phenotypic differences were observed between μ-calpain knockout (KO) and wild type (WT) mice, including nutrient accretion and fiber type differences. These changes were particularly evident as the animals aged. Thus, we utilized 18 mice (9 KO and 9 WT) to compare transcript abundance to identify differentially expressed genes (DEGs) at 52 wk of age...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29773792/mxb-is-an-interferon-induced-restriction-factor-of-human-herpesviruses
#3
Michel Crameri, Michael Bauer, Nicole Caduff, Raphael Walker, Fiona Steiner, Francesca D Franzoso, Cornelia Gujer, Karin Boucke, Talissa Kucera, Andrea Zbinden, Christian Münz, Cornel Fraefel, Urs F Greber, Jovan Pavlovic
The type I interferon (IFN) system plays an important role in controlling herpesvirus infections, but it is unclear which IFN-mediated effectors interfere with herpesvirus replication. Here we report that human myxovirus resistance protein B (MxB, also designated Mx2) is a potent human herpesvirus restriction factor in the context of IFN. We demonstrate that ectopic MxB expression restricts a range of herpesviruses from the Alphaherpesvirinae and Gammaherpesvirinae, including herpes simplex virus 1 and 2 (HSV-1 and HSV-2), and Kaposi's sarcoma-associated herpesvirus (KSHV)...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773643/the-transcription-factor-bhlhe40-is-a-switch-of-inflammatory-versus-antiinflammatory-th1-cell-fate-determination
#4
Fang Yu, Suveena Sharma, Dragana Jankovic, Rama Krishna Gurram, Pan Su, Gangqing Hu, Rao Li, Sadiye Rieder, Keji Zhao, Bing Sun, Jinfang Zhu
Type 1 T helper (Th1) cells play a critical role in host defense against intracellular pathogens and in autoimmune diseases by producing a key inflammatory cytokine interferon (IFN)-γ; some Th1 cells can also be antiinflammatory through producing IL-10. However, the molecular switch for regulating the differentiation of inflammatory and antiinflammatory Th1 cells is still elusive. Here, we show that Bhlhe40 -deficient CD4 Th1 cells produced less IFN-γ but substantially more IL-10 than wild-type Th1 cells both in vitro and in vivo...
May 17, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29765910/a-promising-ifn-deficient-system-to-manufacture-ifn-sensitive-influenza-vaccine-virus
#5
Can Chen, Wenhui Fan, Jing Li, Weinan Zheng, Shuang Zhang, Limin Yang, Di Liu, Wenjun Liu, Lei Sun
Interferon (IFN)-sensitive and replication-incompetent influenza viruses are likely to be the alternatives to inactivated and attenuated virus vaccines. Some IFN-sensitive influenza vaccine candidates with modified non-structural protein 1 (NS1) are highly attenuated in IFN-competent hosts but induce robust antiviral immune responses. However, little research has been done on the manufacturability of these IFN-sensitive vaccine viruses. Here, RIG-I-knockout 293T cells were used to package the IFN-sensitive influenza A/WSN/33 (H1N1) virus expressing the mutant NS1 R38A/K41A...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29764952/samhd1-phosphorylation-coordinates-the-anti-hiv-1-response-by-diverse-interferons-and-tyrosine-kinase-inhibition
#6
Matthew A Szaniawski, Adam M Spivak, James E Cox, Jonathan L Catrow, Timothy Hanley, Elizabeth S C P Williams, Michel J Tremblay, Alberto Bosque, Vicente Planelles
Macrophages are susceptible to human immunodeficiency virus type 1 (HIV-1) infection despite abundant expression of antiviral proteins. Perhaps the most important antiviral protein is the restriction factor sterile alpha motif domain and histidine/aspartic acid domain-containing protein 1 (SAMHD1). We investigated the role of SAMHD1 and its phospho-dependent regulation in the context of HIV-1 infection in primary human monocyte-derived macrophages and the ability of various interferons (IFNs) and pharmacologic agents to modulate SAMHD1...
May 15, 2018: MBio
https://www.readbyqxmd.com/read/29764681/plasmid-pcdna3-1-s11-constructed-based-on-the-s11-segment-of-grass-carp-reovirus-as-dna-vaccine-provides-immune-protection
#7
Yan Gao, Chao Pei, Xiaoying Sun, Chao Zhang, Li Li, Xianghui Kong
Although some commercial vaccines against grass carp reovirus (GCRV) are available, given the many varieties of GCRV and limited types of vaccines, the disease caused by GCRV remains a major problem, which leads to economic losses in grass carp aquaculture. A reovirus strain (GCRV-HN14) was recently isolated from local diseased fish in our laboratory. The S11 segment of GCRV-HN14 was speculated to encode the virus capsid protein VP35. In our study, the S11 segment was cloned into the eukaryotic expression vector pcDNA3...
May 12, 2018: Vaccine
https://www.readbyqxmd.com/read/29762170/a-compartmentalized-type-i-interferon-response-in-the-gut-during-chronic-hiv-1-infection-is-associated-with-immunopathogenesis
#8
Stephanie M Dillon, Kejun Guo, Gregory L Austin, Sara Gianella, Phillip A Engen, Ece A Mutlu, John Losurdo, Garth Swanson, Prachi Chakradeo, Ali Keshavarzian, Alan L Landay, Mario Santiago, Cara Wilson
OBJECTIVE(S): Type I IFN (IFN-I) responses confer both protective and pathogenic effects in persistent virus infections. IFN-I diversity, stage of infection and tissue compartment may account for this dichotomy. The gut is a major site of early HIV-1 replication and microbial translocation, but the nature of the IFN-I response in this compartment remains unclear. DESIGN: Samples were obtained from two IRB-approved cross-sectional studies. The first study included individuals with chronic, untreated HIV-1 infection (n = 24) and age/gender balanced uninfected controls (n = 14)...
May 11, 2018: AIDS
https://www.readbyqxmd.com/read/29760876/rinck-mediated-monoubiquitination-of-cgas-promotes-antiviral-innate-immune-responses
#9
Zhao-Shan Liu, Zi-Yu Zhang, Hong Cai, Ming Zhao, Jie Mao, Jiang Dai, Tian Xia, Xue-Min Zhang, Tao Li
Background: As an important danger signal, the presence of DNA in cytoplasm triggers potent immune responses. Cyclic GMP-AMP synthase (cGAS) is a recently characterized key sensor for cytoplasmic DNA. The engagement of cGAS with DNA leads to the synthesis of a second messenger, cyclic GMP-AMP (cGAMP), which binds and activates the downstream adaptor protein STING to promote type I interferon production. Although cGAS has been shown to play a pivotal role in innate immunity, the exact regulation of cGAS activation is not fully understood...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29760540/ambiguous-roles-of-innate-lymphoid-cells-in-chronic-development-of-liver-diseases
#10
REVIEW
Yue Shen, Jing Li, Si-Qi Wang, Wei Jiang
Innate lymphoid cells (ILCs) are defined as a distinct arm of innate immunity. According to their profile of secreted cytokines and lineage-specific transcriptional factors, ILCs can be categorized into the following three groups: group 1 ILCs (including natural killer (NK) cells and ILC1s) are dependent on T-bet and can produce interferon-γ; group 2 ILCs (ILC2s) are dependent on GATA3 and can produce type 2 cytokines, including interleukin (IL)-5 and IL-13; and, group 3 ILCs (including lymphoid tissue-like cells and ILC3s) are dependent on RORγt and can produce IL-22 and IL-17...
May 14, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29759327/immunotherapy-responsive-childhood-neurodegeneration-with-systemic-and-central-nervous-system-inflammation
#11
Mario Sa, Yael Hacohen, Lucy Alderson, W K Kling Chong, Glenn Anderson, Thomas S Jacques, David Neubauer, Elzbieta Szczepanik, Ming Lim, Marios Kaliakatsos
Subacute neuroregression in association with raised neopterin and overexpression of interferon stimulated genes (ISGs) could indicate a type 1 interferonopathy. Here we describe a novel immunotherapy-responsive, clinico-immunological and imaging phenotype with evidence of innate immune activation. Three children (patient 1: 22-month-old boy; patient 2: 5-year-old girl; patient 3: 4-year-old girl) presented with asymmetric bilateral mixed dystonia and spasticity, regression in language (expressive more than receptive) and bulbar symptoms with no evidence of seizures...
April 27, 2018: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/29753657/irf-1-rig-i-and-mda5-display-potent-antiviral-activities-against-norovirus-coordinately-induced-by-different-types-of-interferons
#12
Wen Dang, Lei Xu, Yuebang Yin, Sunrui Chen, Wenshi Wang, Mohamad S Hakim, Kyeong-Ok Chang, Maikel P Peppelenbosch, Qiuwei Pan
Norovirus represents the main cause of acute nonbacterial gastroenteritis worldwide. In immunocompromised patients, it bears high risk of causing chronic infection with significant morbidity and mortality. The lack of specific treatment prompts the development of anti-norovirus agents. In this study, we have investigated the role of interferon (IFN) response and evaluated antiviral activities of different IFNs against human norovirus (HuNoV) replication using a HuNoV replicon model. We found that HuNoV RNA replication was sensitive to all types of IFNs, including IFNα (type I), IFNγ (type II), IFNλ1 and 3 (type III)...
May 10, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29752586/comparison-of-tracheal-reconstruction-with-allograft-fresh-xenograft-and-artificial-trachea-scaffold-in-a-rabbit-model
#13
Jae Yeon Lee, Jeong Hun Park, Dong-Woo Cho
This study evaluated the possibility of tracheal reconstruction with allograft, pig-to-rabbit fresh xenograft or use of a tissue-engineered trachea, and compared acute rejection of three different transplanted tracheal segments in rabbits. Eighteen healthy New Zealand White rabbits weighing 2.5-3.1 kg were transplanted with three different types of trachea substitutes. Two rabbits and two alpha 1, 3-galactosyltransferase gene-knockout pigs weighing 5 kg were used as donors. The rabbits were divided into three groups: an allograft control group consisting of rabbit-to-rabbit allotransplantation animals (n = 6), a fresh xenograft group consisting of pig-to-rabbit xenotransplantation animals (n = 6), and an artificial trachea scaffold group (n = 6)...
May 12, 2018: Journal of Artificial Organs: the Official Journal of the Japanese Society for Artificial Organs
https://www.readbyqxmd.com/read/29751735/identification-of-compounds-that-prolong-type-i-interferon-signaling-as-potential-vaccine-adjuvants
#14
Nikunj M Shukla, Kei-Ichiro Arimoto, Shiyin Yao, Jun-Bao Fan, Yue Zhang, Fumi Sato-Kaneko, Fitzgerald S Lao, Tadashi Hosoya, Karen Messer, Minya Pu, Howard B Cottam, Dennis A Carson, Tomoko Hayashi, Dong-Er Zhang, Maripat Corr
Vaccines are reliant on adjuvants to enhance the immune stimulus, and type I interferons (IFNs) have been shown to be beneficial in augmenting this response. We were interested in identifying compounds that would sustain activation of an endogenous type I IFN response as a co-adjuvant. We began with generation of a human monocytic THP-1 cell line with an IFN-stimulated response element (ISRE)-β-lactamase reporter construct for high-throughput screening. Pilot studies were performed to optimize the parameters and conditions for this cell-based Förster resonance energy transfer (FRET) reporter assay for sustaining an IFN-α-induced ISRE activation signal...
May 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29751576/thymoquinone-suppresses-irf-3-mediated-expression-of-type-i-interferons-via-suppression-of-tbk1
#15
Nur Aziz, Young-Jin Son, Jae Youl Cho
Interferon regulatory factor (IRF)-3 is known to have a critical role in viral and bacterial innate immune responses by regulating the production of type I interferon (IFN). Thymoquinone (TQ) is a compound derived from black cumin ( Nigella sativa L.) and is known to regulate immune responses by affecting transcription factors associated with inflammation, including nuclear factor-κB (NF-κB) and activator protein-1 (AP-1). However, the role of TQ in the IRF-3 signaling pathway has not been elucidated...
May 3, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29748576/autophagy-diminishes-the-early-interferon-%C3%AE-response-to-influenza-a-virus-resulting-in-differential-expression-of-interferon-stimulated-genes
#16
Brieuc P Perot, Jeremy Boussier, Nader Yatim, Jeremy S Rossman, Molly A Ingersoll, Matthew L Albert
Influenza A virus (IAV) infection perturbs metabolic pathways such as autophagy, a stress-induced catabolic pathway that crosstalks with cellular inflammatory responses. However, the impact of autophagy perturbation on IAV gene expression or host cell responses remains disputed. Discrepant results may be a reflection of in vivo studies using cell-specific autophagy-related (Atg) gene-deficient mouse strains, which do not delineate modification of developmental programmes from more proximal effects on inflammatory response...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29748386/frequent-irf1-binding-at-remote-elements-without-histone-modification
#17
Mohamed Abou El Hassan, Katherine Huang, Zhaodong Xu, Tao Yu, Rod Bremner
Transcriptional activators bind DNA and recruit cofactors to modify chromatin.  The extent to which these two events are separable is unclear.  Here, using a custom ChIP tiling array to map chromatin modifications, we show that Interferon-γ-induced DNA-binding of signal transducer and activator of transcription 1 (STAT1), typically associated with the transcription factor IFN regulatory factor 1 (IRF1), causes histone acetylation (H3ac, H4ac). In contrast, among IRF1 sites lacking concomitant STAT1 recruitment, only 25% underwent inducible histone acetylation, 31% exhibited constitutive histone acetylation, and 44% had no histone acetylation...
May 10, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29743377/equine-myxovirus-resistance-protein-2-restricts-lentiviral-replication-by-blocking-nuclear-uptake-of-capsid-protein
#18
Shuang Ji, Lei Na, Huiling Ren, Yujie Wang, Xiaojun Wang
Human Myxovirus resistance 2 (huMxB) has been shown to be a determinant type I interferon-induced host factor involved in the inhibition of HIV-1 as well as many other primate lentiviruses. This blocking occurs after the reverse transcription of viral RNA and ahead of the integration into the host DNA, which is closely connected to the ability of the protein to bind the viral capsid. To date, Mx2s derived from non-primate animals have shown no capacity for HIV-1 suppression. In this study, we examined the restrictive effect of equine Mx2 (eqMx2) on both the equine infectious anemia virus (EIAV) and HIV-1 and investigated possible mechanisms for its specific function...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29743358/the-chromatin-remodeling-factor-spoc1-acts-as-a-cellular-restriction-factor-against-human-cytomegalovirus-by-repressing-the-major-immediate-early-promoter
#19
Anna Reichel, Anne-Charlotte Stilp, Myriam Scherer, Nina Reuter, Sören Lukassen, Bahram Kasmapour, Sabrina Schreiner, Luka Cicin-Sain, Andreas Winterpacht, Thomas Stamminger
The cellular protein SPOC1 (survival time-associated PHD finger protein in ovarian cancer 1) acts as a regulator of chromatin structure and DNA damage response. It binds H3K4me2/3 containing chromatin and promotes DNA condensation by recruiting corepressors such as KAP-1 and H3K9 methyltransferases. Previous studies identified SPOC1 as a restriction factor against human adenovirus (HAdV) infection that is antagonized by E1B-55K/E4orf6-dependent proteasomal degradation. Here, we demonstrate that, in contrast to HAdV-infected cells, SPOC1 is transiently upregulated during the early phase of HCMV replication...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29742458/interferons-type-ii-and-their-receptors-r1-and-r2-in-fish-species-evolution-structure-and-function
#20
Jiří Zahradník, Lucie Kolářová, Hana Pařízková, Petr Kolenko, Bohdan Schneider
Interferon gamma (IFN-γ) is one of the key players in the immune system of vertebrates. The evolution and properties of IFN-γ and its receptors in fish species are of special interest as they point to the origin of innate immunity in vertebrates. We studied the phylogeny, biophysical and structural properties of IFN-γ and its receptors. Our phylogeny analysis suggests the existence of two groups of IFN-γ related proteins, one specific for Acanthomorpha, the other for Cypriniformes, Characiformes and Siluriformes...
May 6, 2018: Fish & Shellfish Immunology
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