Mechanisms of HIV-1 Restriction by the Host Protein SAMHD1
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Non-Primate Lentiviral Vectors and Their Applications in Gene Therapy for Ocular Disorders
viruses Review Non-Primate Lentiviral Vectors and Their Applications in Gene Therapy for Ocular Disorders Vincenzo Cavalieri 1,2,* ID , Elena Baiamonte 3 and Melania Lo Iacono 3 1 Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze Edificio 16, 90128 Palermo, Italy 2 Advanced Technologies Network (ATeN) Center, University of Palermo, Viale delle Scienze Edificio 18, 90128 Palermo, Italy 3 Campus of Haematology Franco e Piera Cutino, Villa Sofia-Cervello Hospital, 90146 Palermo, Italy; [email protected] (E.B.); [email protected] (M.L.I.) * Correspondence: [email protected] Received: 30 April 2018; Accepted: 7 June 2018; Published: 9 June 2018 Abstract: Lentiviruses have a number of molecular features in common, starting with the ability to integrate their genetic material into the genome of non-dividing infected cells. A peculiar property of non-primate lentiviruses consists in their incapability to infect and induce diseases in humans, thus providing the main rationale for deriving biologically safe lentiviral vectors for gene therapy applications. In this review, we first give an overview of non-primate lentiviruses, highlighting their common and distinctive molecular characteristics together with key concepts in the molecular biology of lentiviruses. We next examine the bioengineering strategies leading to the conversion of lentiviruses into recombinant lentiviral vectors, discussing their potential clinical applications in ophthalmological research. Finally, we highlight the invaluable role of animal organisms, including the emerging zebrafish model, in ocular gene therapy based on non-primate lentiviral vectors and in ophthalmology research and vision science in general. Keywords: FIV; EIAV; BIV; JDV; VMV; CAEV; lentiviral vector; gene therapy; ophthalmology; zebrafish 1. -
Analysis of Gene–Environment Interactions in Postnatal
– Analysis of gene environment interactions in postnatal INAUGURAL ARTICLE development of the mammalian intestine Seth Rakoff-Nahouma,b,c,1, Yong Kongd, Steven H. Kleinsteine, Sathish Subramanianf, Philip P. Ahernf, Jeffrey I. Gordonf, and Ruslan Medzhitova,b,1 aHoward Hughes Medical Institute, bDepartment of Immunobiology, dDepartment of Molecular Biophysics and Biochemistry, W. M. Keck Foundation Biotechnology Resource Laboratory, and eInterdepartmental Program in Computational Biology and Bioinformatics and Department of Pathology, Yale University School of Medicine, New Haven, CT 06510; fCenter for Genome Sciences and Systems Biology, Washington University School of Medicine in St. Louis, St. Louis, MO 63108; and cDivision of Infectious Diseases, Department of Medicine, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115 This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected in 2010. Contributed by Ruslan Medzhitov, December 31, 2014 (sent for review December 25, 2014; reviewed by Alexander V. Chervonsky and Alexander Y. Rudensky) Unlike mammalian embryogenesis, which takes place in the relatively immediately after birth, the intestine is exposed to mother’s milk predictable and stable environment of the uterus, postnatal develop- and undergoes initial colonization with microorganisms. Second, ment can be affected by a multitude of highly variable environmental after weaning, the intestinal tract becomes exposed to solid foods factors, including diet, exposure to noxious substances, and micro- and is no longer exposed to mother’s milk components, the host organisms. Microbial colonization of the intestine is thought to play a immune system matures, and the microbiota shifts. particularly important role in postnatal development of the gastroin- Although it is widely recognized that these transitions have testinal, metabolic, and immune systems. -
Supplement 1 Overview of Dystonia Genes
Supplement 1 Overview of genes that may cause dystonia in children and adolescents Gene (OMIM) Disease name/phenotype Mode of inheritance 1: (Formerly called) Primary dystonias (DYTs): TOR1A (605204) DYT1: Early-onset generalized AD primary torsion dystonia (PTD) TUBB4A (602662) DYT4: Whispering dystonia AD GCH1 (600225) DYT5: GTP-cyclohydrolase 1 AD deficiency THAP1 (609520) DYT6: Adolescent onset torsion AD dystonia, mixed type PNKD/MR1 (609023) DYT8: Paroxysmal non- AD kinesigenic dyskinesia SLC2A1 (138140) DYT9/18: Paroxysmal choreoathetosis with episodic AD ataxia and spasticity/GLUT1 deficiency syndrome-1 PRRT2 (614386) DYT10: Paroxysmal kinesigenic AD dyskinesia SGCE (604149) DYT11: Myoclonus-dystonia AD ATP1A3 (182350) DYT12: Rapid-onset dystonia AD parkinsonism PRKRA (603424) DYT16: Young-onset dystonia AR parkinsonism ANO3 (610110) DYT24: Primary focal dystonia AD GNAL (139312) DYT25: Primary torsion dystonia AD 2: Inborn errors of metabolism: GCDH (608801) Glutaric aciduria type 1 AR PCCA (232000) Propionic aciduria AR PCCB (232050) Propionic aciduria AR MUT (609058) Methylmalonic aciduria AR MMAA (607481) Cobalamin A deficiency AR MMAB (607568) Cobalamin B deficiency AR MMACHC (609831) Cobalamin C deficiency AR C2orf25 (611935) Cobalamin D deficiency AR MTRR (602568) Cobalamin E deficiency AR LMBRD1 (612625) Cobalamin F deficiency AR MTR (156570) Cobalamin G deficiency AR CBS (613381) Homocysteinuria AR PCBD (126090) Hyperphelaninemia variant D AR TH (191290) Tyrosine hydroxylase deficiency AR SPR (182125) Sepiaterine reductase -
Table 2. Significant
Table 2. Significant (Q < 0.05 and |d | > 0.5) transcripts from the meta-analysis Gene Chr Mb Gene Name Affy ProbeSet cDNA_IDs d HAP/LAP d HAP/LAP d d IS Average d Ztest P values Q-value Symbol ID (study #5) 1 2 STS B2m 2 122 beta-2 microglobulin 1452428_a_at AI848245 1.75334941 4 3.2 4 3.2316485 1.07398E-09 5.69E-08 Man2b1 8 84.4 mannosidase 2, alpha B1 1416340_a_at H4049B01 3.75722111 3.87309653 2.1 1.6 2.84852656 5.32443E-07 1.58E-05 1110032A03Rik 9 50.9 RIKEN cDNA 1110032A03 gene 1417211_a_at H4035E05 4 1.66015788 4 1.7 2.82772795 2.94266E-05 0.000527 NA 9 48.5 --- 1456111_at 3.43701477 1.85785922 4 2 2.8237185 9.97969E-08 3.48E-06 Scn4b 9 45.3 Sodium channel, type IV, beta 1434008_at AI844796 3.79536664 1.63774235 3.3 2.3 2.75319499 1.48057E-08 6.21E-07 polypeptide Gadd45gip1 8 84.1 RIKEN cDNA 2310040G17 gene 1417619_at 4 3.38875643 1.4 2 2.69163229 8.84279E-06 0.0001904 BC056474 15 12.1 Mus musculus cDNA clone 1424117_at H3030A06 3.95752801 2.42838452 1.9 2.2 2.62132809 1.3344E-08 5.66E-07 MGC:67360 IMAGE:6823629, complete cds NA 4 153 guanine nucleotide binding protein, 1454696_at -3.46081884 -4 -1.3 -1.6 -2.6026947 8.58458E-05 0.0012617 beta 1 Gnb1 4 153 guanine nucleotide binding protein, 1417432_a_at H3094D02 -3.13334396 -4 -1.6 -1.7 -2.5946297 1.04542E-05 0.0002202 beta 1 Gadd45gip1 8 84.1 RAD23a homolog (S. -
The Expression of Human Endogenous Retroviruses Is Modulated by the Tat Protein of HIV‐1
The Expression of Human Endogenous Retroviruses is modulated by the Tat protein of HIV‐1 by Marta Jeannette Gonzalez‐Hernandez A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Immunology) in The University of Michigan 2012 Doctoral Committee Professor David M. Markovitz, Chair Professor Gary Huffnagle Professor Michael J. Imperiale Associate Professor David J. Miller Assistant Professor Akira Ono Assistant Professor Christiane E. Wobus © Marta Jeannette Gonzalez‐Hernandez 2012 For my family and friends, the most fantastic teachers I have ever had. ii Acknowledgements First, and foremost, I would like to thank David Markovitz for his patience and his scientific and mentoring endeavor. My time in the laboratory has been an honor and a pleasure. Special thanks are also due to all the members of the Markovitz laboratory, past and present. It has been a privilege, and a lot of fun, to work near such excellent scientists and friends. You all have a special place in my heart. I would like to thank all the members of my thesis committee for all the valuable advice, help and jokes whenever needed. Our collaborators from the Bioinformatics Core, particularly James Cavalcoli, Fan Meng, Manhong Dai, Maureen Sartor and Gil Omenn gave generous support, technical expertise and scientific insight to a very important part of this project. Thank you. Thanks also go to Mariana Kaplan’s and Akira Ono’s laboratory for help with experimental designs and for being especially generous with time and reagents. iii Table of Contents Dedication ............................................................................................................................ ii Acknowledgements ............................................................................................................. iii List of Figures ................................................................................................................... -
Datasheet: VMA00139 Product Details
Datasheet: VMA00139 Description: MOUSE ANTI SAMHD1 Specificity: SAMHD1 Format: Purified Product Type: PrecisionAb™ Monoclonal Clone: OTI1F6 Isotype: IgG1 Quantity: 100 µl Product Details Applications This product has been reported to work in the following applications. This information is derived from testing within our laboratories, peer-reviewed publications or personal communications from the originators. Please refer to references indicated for further information. For general protocol recommendations, please visit www.bio-rad-antibodies.com/protocols. Yes No Not Determined Suggested Dilution Western Blotting 1/1000 PrecisionAb antibodies have been extensively validated for the western blot application. The antibody has been validated at the suggested dilution. Where this product has not been tested for use in a particular technique this does not necessarily exclude its use in such procedures. Further optimization may be required dependant on sample type. Target Species Human Product Form Purified IgG - liquid Preparation Mouse monoclonal antibody purified by affinity chromatography from ascites. Buffer Solution Phosphate buffered saline Preservative 0.09% Sodium Azide (NaN3) Stabilisers 1% Bovine Serum Albumin 50% Glycerol Immunogen Full length recombinant human SAMHD1 (NP_056289) produced in HEK293T cells External Database Links UniProt: Q9Y3Z3 Related reagents Entrez Gene: 25939 SAMHD1 Related reagents Synonyms MOP5 Page 1 of 2 Specificity Mouse anti Human SAMHD1 antibody recognizes the deoxynucleoside triphosphate triphosphohydrolase SAMHD1, also known as SAM domain and HD domain-containing protein 1, dNTPase, dendritic cell-derived IFNG-induced protein, deoxynucleoside triphosphate triphosphohydrolase SAMHD1 and monocyte protein 5. SAMHD1 may play a role in regulation of the innate immune response. The encoded protein is upregulated in response to viral infection and may be involved in mediation of tumor necrosis factor-alpha proinflammatory responses. -
HIV 101: Pathogenesis and Treatment
HIV 101: Pathogenesis and Treatment Stephen Raffanti MD MPH Professor of Medicine Vanderbilt University School of Medicine . Dr. Raffanti has no financial disclosures to make. Objectives . After this presentation the attendee should be able to: . Describe current issues in the epidemiology of the HIV epidemic. Describe the life cycle of HIV; . Describe the way that HIV interacts with its host, producing disease. Describe the principles of treatment. Describe Acute HIV infection . Describe the initial evaluation of an HIV infected patient Testing, linkage to care, effective treatment and effective PrEP could stop the epidemic today. Percentages of Diagnoses of HIV Infection among Adults and Adolescents, by Region and Population of Area of Residence, 2015—United States Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. Data for the year 2015 are preliminary and based on 6 months reporting delay. Data exclude persons whose county of residence is unknown. Percentages of Diagnoses of HIV Infection among Adults and Adolescents, by Population of Area of Residence and Age at Diagnosis, 2015—United States Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. Data for the year 2015 are preliminary and based on 6 months reporting delay. Data exclude persons whose county of residence is unknown. Diagnoses of HIV Infection among Men Who Have Sex with Men, by Age Group, 2010–2014—United States and 6 Dependent Areas Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All displayed data have been statistically adjusted to account for reporting delays and missing transmission category, but not for incomplete reporting. -
Supplementary Materials
1 Supplementary Materials: Supplemental Figure 1. Gene expression profiles of kidneys in the Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice. (A) A heat map of microarray data show the genes that significantly changed up to 2 fold compared between Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice (N=4 mice per group; p<0.05). Data show in log2 (sample/wild-type). 2 Supplemental Figure 2. Sting signaling is essential for immuno-phenotypes of the Fcgr2b-/-lupus mice. (A-C) Flow cytometry analysis of splenocytes isolated from wild-type, Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice at the age of 6-7 months (N= 13-14 per group). Data shown in the percentage of (A) CD4+ ICOS+ cells, (B) B220+ I-Ab+ cells and (C) CD138+ cells. Data show as mean ± SEM (*p < 0.05, **p<0.01 and ***p<0.001). 3 Supplemental Figure 3. Phenotypes of Sting activated dendritic cells. (A) Representative of western blot analysis from immunoprecipitation with Sting of Fcgr2b-/- mice (N= 4). The band was shown in STING protein of activated BMDC with DMXAA at 0, 3 and 6 hr. and phosphorylation of STING at Ser357. (B) Mass spectra of phosphorylation of STING at Ser357 of activated BMDC from Fcgr2b-/- mice after stimulated with DMXAA for 3 hour and followed by immunoprecipitation with STING. (C) Sting-activated BMDC were co-cultured with LYN inhibitor PP2 and analyzed by flow cytometry, which showed the mean fluorescence intensity (MFI) of IAb expressing DC (N = 3 mice per group). 4 Supplemental Table 1. Lists of up and down of regulated proteins Accession No. -
SAMHD1 and the Innate Immune Response to Cytosolic DNA During
Available online at www.sciencedirect.com ScienceDirect SAMHD1 and the innate immune response to cytosolic DNA during DNA replication Flavie Coquel, Christoph Neumayer, Yea-Lih Lin and Philippe Pasero Cytosolic DNA of endogenous or exogenous origin is sensed by double-stranded DNA (dsDNA) in a sequence-indepen- the cGAS-STING pathway to activate innate immune dent manner and produces cyclic-GMP-AMP. This sec- responses. Besides microbial DNA, this pathway detects self- ond messenger binds STING and induces TBK1 activa- DNA in the cytoplasm of damaged or abnormal cells and plays tion, IRF3 phosphorylation and induction of type I IFNs a central role in antitumor immunity. The mechanism by which and other cytokine genes [1,2]. cytosolic DNA accumulates under genotoxic stress conditions is currently unclear, but recent studies on factors mutated in the Besides pathogens, the innate immune system also Aicardi-Goutie` res syndrome cells, such as SAMHD1, RNase responds to tissue damage by sensing damage-associated H2 and TREX1, are shedding new light on this key process. In molecular patterns, including cytosolic DNA of endoge- particular, these studies indicate that the rupture of micronuclei nous origin. The cGAS-STING pathway is activated by and the release of ssDNA fragments during the processing of cytosolic DNA accumulating after ionizing radiation [3] stalled replication forks and chromosome breaks represent or exposure to a variety of chemotherapeutic agents potent inducers of the cGAS-STING pathway. targeting DNA replication forks [4–6]. -
VMC 321: Systematic Veterinary Virology Retroviridae Retro: from Latin Retro,"Backwards”
VMC 321: Systematic Veterinary Virology Retroviridae Retro: from Latin retro,"backwards” - refers to the activity of reverse RETROVIRIDAE transcriptase and the transfer of genetic information from RNA to DNA. Retroviruses Viral RNA Viral DNA Viral mRNA, genome (integrated into host genome) Reverse (retro) transfer of genetic information Usually, well adapted to their hosts Endogenous retroviruses • RNA viruses • single stranded, positive sense, enveloped, icosahedral. • Distinguished from all other RNA viruses by presence of an unusual enzyme, reverse transcriptase. Retroviruses • Retro = reversal • RNA is serving as a template for DNA synthesis. • One genera of veterinary interest • Alpharetrovirus • • Family - Retroviridae • Subfamily - Orthoretrovirinae [Ortho: from Greek orthos"straight" • Genus -. Alpharetrovirus • Genus - Betaretrovirus Family- • Genus - Gammaretrovirus • Genus - Deltaretrovirus Retroviridae • Genus - Lentivirus [ Lenti: from Latin lentus, "slow“ ]. • Genus - Epsilonretrovirus • Subfamily - Spumaretrovirinae • Genus - Spumavirus Retroviridae • Subfamily • Orthoretrovirinae • Genus • Alpharetrovirus Alpharetrovirus • Species • Avian leukosis virus(ALV) • Rous sarcoma virus (RSV) • Avian myeloblastosis virus (AMV) • Fujinami sarcoma virus (FuSV) • ALVs have been divided into 10 envelope subgroups - A , B, C, D, E, F, G, H, I & J based on • host range Avian • receptor interference patterns • neutralization by antibodies leukosis- • subgroup A to E viruses have been divided into two groups sarcoma • Noncytopathic (A, C, and E) • Cytopathic (B and D) virus (ALV) • Cytopathic ALVs can cause a transient cytotoxicity in 30- 40% of the infected cells 1. The viral envelope formed from host cell membrane; contains 72 spiked knobs. 2. These consist of a transmembrane protein TM (gp 41), which is linked to surface protein SU (gp 120) that binds to a cell receptor during infection. 3. The virion has cone-shaped, icosahedral core, Structure containing the major capsid protein 4. -
SAMHD1 Is Recurrently Mutated in T-Cell Prolymphocytic Leukemia
SAMHD1 is recurrently mutated in T-cell prolymphocytic leukemia Patricia Johansson, University of Duisburg-Essen Ludger Klein-Hitpass, University of Duisburg-Essen Axel Choidas, Lead Discovery Center GmbH Peter Habenberger, Lead Discovery Center GmbH Bijan Mahboubi, Emory University Baek Kim, Emory University Anke Bergmann, Christian-Albrechts-University Kiel Rene Scholtysik, University of Duisburg-Essen Martina Brauser, University of Duisburg-Essen Anna Lollies, University of Duisburg-Essen Only first 10 authors above; see publication for full author list. Journal Title: Blood Cancer Journal Volume: Volume 8, Number 1 Publisher: Nature Publishing Group | 2018-01-19, Pages 11-11 Type of Work: Article | Final Publisher PDF Publisher DOI: 10.1038/s41408-017-0036-5 Permanent URL: https://pid.emory.edu/ark:/25593/s8785 Final published version: http://dx.doi.org/10.1038/s41408-017-0036-5 Copyright information: © 2018 The Author(s). This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/). Accessed September 29, 2021 6:39 AM EDT Johansson et al. Blood Cancer Journal (2018) 8:11 DOI 10.1038/s41408-017-0036-5 Blood Cancer Journal ARTICLE Open Access SAMHD1 is recurrently mutated in T-cell prolymphocytic leukemia Patricia Johansson1,2, Ludger Klein-Hitpass2,AxelChoidas3, Peter Habenberger3, Bijan Mahboubi4,BaekKim4, Anke Bergmann5,RenéScholtysik2, Martina Brauser2, Anna Lollies2,ReinerSiebert5,6, Thorsten Zenz7,8, Ulrich Dührsen1, Ralf Küppers2,8 and Jan Dürig1,8 Abstract T-cell prolymphocytic leukemia (T-PLL) is an aggressive malignancy with a median survival of the patients of less than two years. -
Phenotypic Spectrum and Long-Term Outcome in Children with Genetic Causes of Early-Onset Epileptic Encephalopathy
Phenotypic Spectrum and Long-term Outcome in Children With Genetic Causes of Early-onset Epileptic Encephalopathy Chunhui Hu Department of Neurology, Children’s Hospital of Fudan University Deying Liu Wuhan Children’s hospital, Tongji Medical college, Huazhong University of Science & Technology Tian Luo Department of Neurology, Children’s Hospital of Fudan University Yi Wang ( [email protected] ) Department of Neurology, Children’s Hospital of Fudan University Zhisheng Liu Wuhan Children’s hospital, Tongji Medical college, Huazhong University of Science & Technology Research Article Keywords: Phenotypic spectrum, Long-term outcome, Genetic, EOEE, Therapy Posted Date: March 11th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-257334/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/23 Abstract Background To explore the clinical phenotype and long-term outcome in children with genetic causes of early-onset epileptic encephalopathies. Methods The clinical data of 118 children between 2010 and 2020 was obtained and analyzed. The whole exome sequencing and copy number variation studies in family were used to nd pathogenic mutations. The conrmed mutations were veried by Sanger sequencing. Results Among 118 patients, 39 patients were diagnosed with DS, 18 were WS, 3 were OS, 3 were EME, 2 were MMFSI, 1 was GLUT1 deciency syndrome, 1 was Pyridoxine dependent epilepsy and 51 were non-symptomatic EOEEs. The initial EEG showed frequent multiple and multifocal sharp waves, spike waves, sharp slow waves or spike slow waves. In the later period, some transformed into infrequent discharging or normal EEG. 112 patients (112/118, 94.9%) showed normal brain MRI, and the remaining 6 had widened extracerebral space.