Origin and Development of Oligoadenylate Synthetase Immune System
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Transcriptomic Profiling of Equine and Viral Genes in Peripheral Blood
pathogens Article Transcriptomic Profiling of Equine and Viral Genes in Peripheral Blood Mononuclear Cells in Horses during Equine Herpesvirus 1 Infection Lila M. Zarski 1, Patty Sue D. Weber 2, Yao Lee 1 and Gisela Soboll Hussey 1,* 1 Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA; [email protected] (L.M.Z.); [email protected] (Y.L.) 2 Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, MI 48824, USA; [email protected] * Correspondence: [email protected] Abstract: Equine herpesvirus 1 (EHV-1) affects horses worldwide and causes respiratory dis- ease, abortions, and equine herpesvirus myeloencephalopathy (EHM). Following infection, a cell- associated viremia is established in the peripheral blood mononuclear cells (PBMCs). This viremia is essential for transport of EHV-1 to secondary infection sites where subsequent immunopathol- ogy results in diseases such as abortion or EHM. Because of the central role of PBMCs in EHV-1 pathogenesis, our goal was to establish a gene expression analysis of host and equine herpesvirus genes during EHV-1 viremia using RNA sequencing. When comparing transcriptomes of PBMCs during peak viremia to those prior to EHV-1 infection, we found 51 differentially expressed equine genes (48 upregulated and 3 downregulated). After gene ontology analysis, processes such as the interferon defense response, response to chemokines, the complement protein activation cascade, cell adhesion, and coagulation were overrepresented during viremia. Additionally, transcripts for EHV-1, EHV-2, and EHV-5 were identified in pre- and post-EHV-1-infection samples. Looking at Citation: Zarski, L.M.; Weber, P.S.D.; micro RNAs (miRNAs), 278 known equine miRNAs and 855 potentially novel equine miRNAs were Lee, Y.; Soboll Hussey, G. -
A Genetic Variant Protective Against Severe COVID-19 Is Inherited from Neandertals
bioRxiv preprint doi: https://doi.org/10.1101/2020.10.05.327197; this version posted October 9, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. A genetic variant protective against severe COVID-19 is inherited from Neandertals Authors Hugo Zeberg1,2* and Svante Pääbo1,3* Affiliations 1 Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany. 2 Department of Neuroscience, Karolinska Institutet, SE-17177 Stockholm, Sweden. 3 Okinawa Institute of Science and Technology, Onna-son, Okinawa 904-0495, Japan. *Corresponding authors: [email protected], [email protected] Abstract It was recently shown that the major genetic risk factor associated with becoming severely ill with COVID-19 when infected by SARS-CoV-2 is inherited from Neandertals. Thanks to new genetic association studies additional risk factors are now being discovered. Using data from a recent genome- wide associations from the Genetics of Mortality in Critical Care (GenOMICC) consortium, we show that a haplotype at a region associated with requiring intensive care is inherited from Neandertals. It encodes proteins that activate enzymes that are important during infections with RNA viruses. As compared to the previously described Neandertal risk haplotype, this Neandertal haplotype is protective against severe COVID-19, is of more moderate effect, and is found at substantial frequencies in all regions of the world outside Africa. 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.10.05.327197; this version posted October 9, 2020. -
Environmental Influences on Endothelial Gene Expression
ENDOTHELIAL CELL GENE EXPRESSION John Matthew Jeff Herbert Supervisors: Prof. Roy Bicknell and Dr. Victoria Heath PhD thesis University of Birmingham August 2012 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. ABSTRACT Tumour angiogenesis is a vital process in the pathology of tumour development and metastasis. Targeting markers of tumour endothelium provide a means of targeted destruction of a tumours oxygen and nutrient supply via destruction of tumour vasculature, which in turn ultimately leads to beneficial consequences to patients. Although current anti -angiogenic and vascular targeting strategies help patients, more potently in combination with chemo therapy, there is still a need for more tumour endothelial marker discoveries as current treatments have cardiovascular and other side effects. For the first time, the analyses of in-vivo biotinylation of an embryonic system is performed to obtain putative vascular targets. Also for the first time, deep sequencing is applied to freshly isolated tumour and normal endothelial cells from lung, colon and bladder tissues for the identification of pan-vascular-targets. Integration of the proteomic, deep sequencing, public cDNA libraries and microarrays, delivers 5,892 putative vascular targets to the science community. -
Oas1b-Dependent Immune Transcriptional Profiles of West Nile
MULTIPARENTAL POPULATIONS Oas1b-dependent Immune Transcriptional Profiles of West Nile Virus Infection in the Collaborative Cross Richard Green,*,† Courtney Wilkins,*,† Sunil Thomas,*,† Aimee Sekine,*,† Duncan M. Hendrick,*,† Kathleen Voss,*,† Renee C. Ireton,*,† Michael Mooney,‡,§ Jennifer T. Go,*,† Gabrielle Choonoo,‡,§ Sophia Jeng,** Fernando Pardo-Manuel de Villena,††,‡‡ Martin T. Ferris,†† Shannon McWeeney,‡,§,** and Michael Gale Jr.*,†,1 *Department of Immunology and †Center for Innate Immunity and Immune Disease (CIIID), University of Washington, § Seattle, Washington 98109, ‡OHSU Knight Cancer Institute, Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, and **Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, Oregon 97239, ††Department of Genetics and ‡‡Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27514 ABSTRACT The oligoadenylate-synthetase (Oas) gene locus provides innate immune resistance to virus KEYWORDS infection. In mouse models, variation in the Oas1b gene influences host susceptibility to flavivirus infection. Oas However, the impact of Oas variation on overall innate immune programming and global gene expression flavivirus among tissues and in different genetic backgrounds has not been defined. We examined how Oas1b acts viral infection in spleen and brain tissue to limit West Nile virus (WNV) susceptibility and disease across a range of innate immunity genetic backgrounds. The laboratory founder strains of the mouse Collaborative Cross (CC) (A/J, C57BL/6J, multiparental 129S1/SvImJ, NOD/ShiLtJ, and NZO/HlLtJ) all encode a truncated, defective Oas1b, whereas the three populations wild-derived inbred founder strains (CAST/EiJ, PWK/PhJ, and WSB/EiJ) encode a full-length OAS1B pro- Multi-parent tein. -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
Microarray Analysis of Novel Genes Involved in HSV- 2 Infection
Microarray analysis of novel genes involved in HSV- 2 infection Hao Zhang Nanjing University of Chinese Medicine Tao Liu ( [email protected] ) Nanjing University of Chinese Medicine https://orcid.org/0000-0002-7654-2995 Research Article Keywords: HSV-2 infection,Microarray analysis,Histospecic gene expression Posted Date: May 12th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-517057/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/19 Abstract Background: Herpes simplex virus type 2 infects the body and becomes an incurable and recurring disease. The pathogenesis of HSV-2 infection is not completely clear. Methods: We analyze the GSE18527 dataset in the GEO database in this paper to obtain distinctively displayed genes(DDGs)in the total sequential RNA of the biopsies of normal and lesioned skin groups, healed skin and lesioned skin groups of genital herpes patients, respectively.The related data of 3 cases of normal skin group, 4 cases of lesioned group and 6 cases of healed group were analyzed.The histospecic gene analysis , functional enrichment and protein interaction network analysis of the differential genes were also performed, and the critical components were selected. Results: 40 up-regulated genes and 43 down-regulated genes were isolated by differential performance assay. Histospecic gene analysis of DDGs suggested that the most abundant system for gene expression was the skin, immune system and the nervous system.Through the construction of core gene combinations, protein interaction network analysis and selection of histospecic distribution genes, 17 associated genes were selected CXCL10,MX1,ISG15,IFIT1,IFIT3,IFIT2,OASL,ISG20,RSAD2,GBP1,IFI44L,DDX58,USP18,CXCL11,GBP5,GBP4 and CXCL9.The above genes are mainly located in the skin, immune system, nervous system and reproductive system. -
(Hies) Infected with Enteric RNA Viruses Identifies Universal and Virus-Specific Epithelial Responses
viruses Article Comparative Analysis of Public RNA-Sequencing Data from Human Intestinal Enteroid (HIEs) Infected with Enteric RNA Viruses Identifies Universal and Virus-Specific Epithelial Responses Roberto J. Cieza 1,2 , Jonathan L. Golob 2, Justin A. Colacino 3,4 and Christiane E. Wobus 1,* 1 Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA; [email protected] 2 Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, MI 48109, USA; [email protected] 3 Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI 48109, USA; [email protected] 4 Department of Nutritional Sciences, University of Michigan, Ann Arbor, MI 48109, USA * Correspondence: [email protected] Abstract: Acute gastroenteritis (AGE) has a significant disease burden on society. Noroviruses, rotaviruses, and astroviruses are important viral causes of AGE but are relatively understudied Citation: Cieza, R.J.; Golob, J.L.; enteric pathogens. Recent developments in novel biomimetic human models of enteric disease are Colacino, J.A.; Wobus, C.E. opening new possibilities for studying human-specific host–microbe interactions. Human intestinal Comparative Analysis of Public enteroids (HIE), which are epithelium-only intestinal organoids derived from stem cells isolated from RNA-Sequencing Data from Human human intestinal biopsy tissues, have been successfully used to culture representative norovirus, Intestinal Enteroid (HIEs) Infected rotavirus, and astrovirus strains. Previous studies investigated host–virus interactions at the intestinal with Enteric RNA Viruses Identifies epithelial interface by individually profiling the epithelial transcriptional response to a member of Universal and Virus-Specific each virus family by RNA sequencing (RNA-seq). -
Interferon-Inducible Antiviral Effectors
REVIEWS Interferon-inducible antiviral effectors Anthony J. Sadler and Bryan R. G. Williams Abstract | Since the discovery of interferons (IFNs), considerable progress has been made in describing the nature of the cytokines themselves, the signalling components that direct the cell response and their antiviral activities. Gene targeting studies have distinguished four main effector pathways of the IFN-mediated antiviral response: the Mx GTPase pathway, the 2′,5′-oligoadenylate-synthetase-directed ribonuclease L pathway, the protein kinase R pathway and the ISG15 ubiquitin-like pathway. As discussed in this Review, these effector pathways individually block viral transcription, degrade viral RNA, inhibit translation and modify protein function to control all steps of viral replication. Ongoing research continues to expose additional activities for these effector proteins and has revealed unanticipated functions of the antiviral response. Pattern-recognition Interferon (IFN) was discovered more than 50 years ago in components of the IFNR signalling pathway (STAT1 receptors as an agent that inhibited the replication of influenza (signal transducer and activator of transcription 1), TYK2 (PRRs). Host receptors that can virus1. The IFN family of cytokines is now recognized as (tyrosine kinase 2) or UNC93B) die of viral disease, with sense pathogen-associated a key component of the innate immune response and the the defect in IFNAR (rather than IFNGR) signalling molecular patterns and initiate 6–9 signalling cascades that lead to first line of defence against viral infection. Accordingly, having the more significant role . an innate immune response. IFNs are currently used therapeutically, with the most The binding of type I IFNs to the IFNAR initiates a These can be membrane bound noteworthy example being the treatment of hepatitis C signalling cascade, which leads to the induction of more (such as Toll-like receptors) or virus (HCV) infection, and they are also used against than 300 IFN-stimulated genes (ISGs)10. -
Type of the Paper (Article
SUPPLEMENTAL FILES 1 Figure S1: There is a strong correlation between expression profiles of RNA isolated from FFPE or fresh tissue. Murine skin (n=5) was sampled after euthanasia. One half of the skin sample was subjected to fresh RNA isolation and the other was fixed in formalin for 16 hours followed by paraffin embedding prior to RNA isolation. Real-time PCR was used to quantitate RNA levels of 10 different genes and the ddct for each gene was plotted for each RNA isolation subtype. Correlation between FFPE and freshly isolated RNA delta-CTs was done via linear regression using GraphPad Prism v.6. Supplemental Table S1. 226 genes regulated in DLE and SCLE (q-value<0.05, absolute log2 fold-change 0.6) having a potential binding site for STAT1 in their promoter Gene symbol ENTREZ DLE fold- DLE SCLE SCLE GENE ID change q-value fold-change q-value FGFR2 2263 0.5 0.0000 0.6 0.0021 CXCL10 3627 39.5 0.0000 22.5 0.0000 CCL5 6352 3.6 0.0000 2.7 0.0000 KRT16 3868 6.4 0.0000 6.1 0.0000 RTP4 64108 1.9 0.0000 1.6 0.0010 PLEK 5341 2.5 0.0000 2.0 0.0000 S100A8 6279 4.5 0.0000 3.4 0.0000 CD9 928 0.6 0.0016 0.6 0.0109 IL2RG 3561 2.9 0.0000 2.3 0.0000 CAT 847 0.6 0.0051 0.6 0.0021 CD3D 915 2.9 0.0000 2.3 0.0000 HLA-DRA 3122 2.3 0.0000 1.9 0.0000 ITGB5 3693 0.7 0.0258 0.6 0.0111 SERPINB3 6317 4.7 0.0000 4.3 0.0000 CD274 29126 1.7 0.0051 1.7 0.0121 IL12RB2 3595 1.7 0.0073 1.6 0.0009 STK17B 9262 1.9 0.0007 1.6 0.0121 ITGAX 3687 2.0 0.0000 1.9 0.0000 ATP5PO 539 0.5 0.0140 0.4 0.0016 SERPINB4 6318 6.5 0.0000 3.1 0.0000 HAVCR2 84868 1.9 0.0000 1.9 0.0000 -
Cancer Upregulated Gene 2, a Novel Oncogene, Confers Resistance to Oncolytic Vesicular Stomatitis Virus Through STAT1-OASL2 Signaling
Cancer Gene Therapy (2013) 20, 125–132 & 2013 Nature America, Inc. All rights reserved 0929-1903/13 www.nature.com/cgt ORIGINAL ARTICLE Cancer upregulated gene 2, a novel oncogene, confers resistance to oncolytic vesicular stomatitis virus through STAT1-OASL2 signaling W Malilas1, SS Koh2, R Srisuttee1, W Boonying1, I-R Cho1, C-S Jeong3, RN Johnston4 and Y-H Chung1 We have recently found a novel oncogene, named cancer upregulated gene 2 (CUG2), which activates Ras and mitogen-activated protein kinases (MAPKs), including ERK, JNK and p38 MAPK. Because activation of these signaling pathways has previously been shown to enhance cancer cell susceptibility to oncolysis by certain viruses, we examined whether vesicular stomatitis virus (VSV) could function as a potential therapeutic agent by efficiently inducing cytolysis in cells transformed by CUG2. Unexpectedly, NIH3T3 cells stably expressing CUG2 (NIH-CUG2) were resistant to VSV because of the activation of signal transducers and activators of transcription 1 (STAT1). The result was supported by evidence showing that suppression of STAT1 with short interference RNA (siRNA) renders cells susceptible to VSV. Furthermore, 20–50 oligoadenylate synthetase-like (OASL) 2 was the most affected by STAT1 expression level among anti-viral proteins and furthermore suppression of OASL2 mRNA level caused NIH-CUG2 cells to succumb to VSV as seen in NIH-CUG2 cells treated with STAT1 siRNA. In addition, Colon26L5 carcinoma cells stably expressing CUG2 (Colon26L5-CUG2) exhibited resistance to VSV, whereas Colon26L5 stably expressing a control vector yielded to VSV infection. Moreover, Colon26L5-CUG2 cells stably suppressing STAT1 succumbed to VSV infection, resulting in apoptosis. -
Full Text (PDF)
medRxiv preprint doi: https://doi.org/10.1101/2020.12.29.20248986; this version posted January 4, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Insights into the molecular mechanism of anticancer drug ruxolitinib repurposable in COVID-19 therapy Manisha Mandal Department of Physiology, MGM Medical College, Kishanganj-855107, India Email: [email protected], ORCID: https://orcid.org/0000-0002-9562-5534 Shyamapada Mandal* Department of Zoology, University of Gour Banga, Malda-732103, India Email: [email protected], ORCID: https://orcid.org/0000-0002-9488-3523 *Corresponding author: Email: [email protected]; [email protected] Abstract Due to non-availability of specific therapeutics against COVID-19, repurposing of approved drugs is a reasonable option. Cytokines imbalance in COVID-19 resembles cancer; exploration of anti-inflammatory agents, might reduce COVID-19 mortality. The current study investigates the effect of ruxolitinib treatment in SARS-CoV-2 infected alveolar cells compared to the uninfected one from the GSE5147507 dataset. The protein-protein interaction network, biological process and functional enrichment of differentially expressed genes were studied using STRING App of the Cytoscape software and R programming tools. The present study indicated that ruxolitinib treatment elicited similar response equivalent to that of SARS-CoV-2 uninfected situation by inducing defense response in host against virus infection by RLR and NOD like receptor pathways. Further, the effect of ruxolitinib in SARS- CoV-2 infection was mainly caused by significant suppression of IFIH1, IRF7 and MX1 genes as well as inhibition of DDX58/IFIH1-mediated induction of interferon- I and -II signalling. -
OASL (H-200): Sc-98313
SAN TA C RUZ BI OTEC HNOL OG Y, INC . OASL (H-200): sc-98313 BACKGROUND PRODUCT OASL (2'-5'-oligoadenylate synthetase-like), also known as p59OASL or TRIP14 Each vial contains 200 µg IgG in 1.0 ml of PBS with < 0.1% sodium azide (thyroid receptor-interacting protein 14), is a 514 amino acid protein that exists and 0.1% gelatin. as 2 alternatively spliced isoforms, designated p56 and p30, and contains 2 ubiquitin-like domains. Expressed in a variety of tissues with highest levels APPLICATIONS present in colon, stomach and testis, OASL interacts with the ligand binding OASL (H-200) is recommended for detection of OASL of human origin by domain of the thyroid receptor (TR) and is able to bind double-stranded RNA Western Blotting (starting dilution 1:200, dilution range 1:100-1:1000), and DNA, possibly playing a role in RNA degradation and the overall inhibi tion immunoprecipitation [1-2 µg per 100-500 µg of total protein (1 ml of cell of protein synthesis. The gene encoding OASL maps to human chromosome 12, lysate)], immunofluorescence (starting dilution 1:50, dilution range 1:50- which encodes over 1,100 genes and comprises approximately 4.5% of the hu- 1:500) and solid phase ELISA (starting dilution 1:30, dilution range 1:30- man genome. Chromosome 12 is associated with a variety of diseases and 1:3000). afflictions, including hypochondrogenesis, achondrogenesis, Kniest dyspla sia, Noonan syndrome and trisomy 12p, which causes facial developmental defects Suitable for use as control antibody for OASL siRNA (h): sc-95857, OASL and seizure disorders.