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Structure and Expression of Class II Defective Herpes Simplex Virus
JOURNAL OF VIROLOGY, Aug. 1982, p. 574-593 Vol. 43, No. 2 0022-538X/82/080574-20$02.00/0 Structure and Expression of Class II Defective Herpes Simplex Virus Genomes Encoding Infected Cell Polypeptide Number 8 HILLA LOCKER,1t NIZA FRENKEL,l* AND IAN HALLIBURTON2 Department ofBiology, The University of Chicago, Chicago, Illinois 60637,1 and Department of Microbiology, University ofLeeds, Leeds, England' Received 12 February 1982/Accepted 13 May 1982 Defective genomes present in serially passaged virus stocks derived from the tsLB2 mutant of herpes simplex virus type 1 were found to consist of repeat units in which sequences from the UL region, within map coordinates 0.356 and 0.429 of standard herpes simplex virus DNA, were covalently linked to sequences from the end of the S component. The major defective genome species consisted of repeat units which were 4.9 x 106 in molecular weight and contained a specific deletion within the UL segment. These tsLB2 defective genomes were stable through more than 35 sequential virus passages. The ratios of defective virus genomes to helper virus genomes present in different passages fluctuated in synchrony with the capacity of the passages to interfere with standard virus replication. Cells infected with passages enriched for defective genomes overpro- duced the infected cell polypeptide number 8, which had previously been mapped within the UL sequences present in the tsLB2 defective genomes. In contrast, the synthesis of most other infected cell polypeptides was delayed and reduced. The abundant synthesis of infected cell polypeptide number 8 followed the , regula- tory pattern, as evident from kinetic studies and from experiments in which cycloheximide, canavanine, and phosphonoacetate were used. -
Oncogenes of DNA Tumor Viruses1
[CANCER RESEARCH 48. 493-496. February I. 1988] Perspectives in Cancer Research Oncogenes of DNA Tumor Viruses1 Arnold J. Levine Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544 Experiments carried out over the past 10-12 years have the cellular oncogenes. It will attempt to identify where more created a field or approach which may properly be termed the information is required or contradictions appear in the devel molecular basis of cancer. One of its major accomplishments oping concepts. Finally, this communication will examine ex has been the identification and understanding of some of the amples of cooperation between oncogenes and other gene prod functions of a group of cancer-causing genes, the oncogenes. ucts which modify the mode of action of the former. If we are The major path to the oncogenes came from the study of cancer- on the right track, then general principles may well emerge. causing viruses. The oncogenes have been recognized and stud Tumor formation in animals or transformation in cell culture ied by two separate but related groups of virologists focusing has been demonstrated with many different DNA-containing upon either the DNA (1) or RNA (2) tumor viruses (they even viruses (1). In most cases it has been possible to identify one or have separate meetings now that these fields have grown so a few viral genes and their products that are responsible for large). From their studies it has become clear that the oncogenes transformation or, in some cases, tumorigenesis. A list of these of each virus type have very different origins. -
Tätigkeitsbericht 2007/2008
Tätigkeitsbericht 2007/2008 8 200 / 7 0 20 Tätigkeitsbericht Stiftung bürgerlichen Rechts Martinistraße 52 · 20251 Hamburg Tel.: +49 (0) 40 480 51-0 · Fax: +49 (0) 40 480 51-103 [email protected] · www.hpi-hamburg.de Impressum Verantwortlich Prof. Dr. Thomas Dobner für den Inhalt Dr. Heinrich Hohenberg Redaktion Dr. Angela Homfeld Dr. Nicole Nolting Grafik & Layout AlsterWerk MedienService GmbH Hamburg Druck Hartung Druck + Medien GmbH Hamburg Titelbild Neu gestaltete Fassade des Seuchenlaborgebäudes Tätigkeitsbericht 2007/2008 Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg Martinistraße 52 · 20251 Hamburg Postfach 201652 · 20206 Hamburg Telefon: +49-40/4 80 51-0 Telefax: +49-40/4 80 51-103 E-Mail: [email protected] Internet: www.hpi-hamburg.de Das Heinrich-Pette-Institut ist Mitglied der Leibniz-Gemeinschaft (WGL) Internet: www.wgl.de Inhaltsverzeichnis Allgemeiner Überblick Vorwort ................................................................................................... 1 Die Struktur des Heinrich-Pette-Instituts .............................................. 2 Modernisierung des HPI erfolgreich abgeschlossen ............................ 4 60 Jahre HPI .............................................................................................. 5 Offen für den Dialog .............................................................................. 6 Preisverleihungen und Ehrungen .......................................................... 8 Personelle Veränderungen in -
Replication of Picornaviruses I
JouRNAL oF VnoLoGy, Dec. 1975, p. 1512-1527 Vol. 16, No. 6 Copyright ©) 1975 American Society for Microbiology Printed in U.SA. Replication of Picornaviruses I. Evidence from In Vitro RNA Synthesis that Poly(A) of the Poliovirus Genome is Genetically Coded KAROLINE DORSCH-HASLER, YOSHIAKI YOGO,' AND ECKARD WIMMER* Department ofMicrobiology, St. Louis University School ofMedicine, St. Louis, Missouri 63104, and Department ofMicrobiology, School ofBasic Health Sciences, State University ofNew York at Stony Brook, Stony Brook, New York 11794 * Received for publication 3 July 1975 A crude replication complex has been isolated from poliovirus-infected HeLa cells and used for synthesis of poliovirus replicative intermediate (RI) RNA, replicative form (RF) RNA, and single-stranded (SS) RNA in vitro. All three classes of virus-specific RNA synthesized in vitro are shown to contain poly(A). Poly(A) of RF and of SS RNA [RF-poly(A) and SS-poly(A)] has a chain length (50 to 70 nucleotides) that is shorter than that of poly(A) of in vivo-synthesized RNAs. Poly(A) of RI [RI-poly(A)], however, is at least 200 nucleotides long and, therefore, larger than poly(A) of RI isolated from HeLa cells 4 h after infection. The crude membrane-bound replication complex contains a terminal adenylate transferase activity that is stimulated by Mn2+ and the addition of an (Ap),AoH primer. This transferase activity is found also in extracts of mock-infected cells. Partial purification of the replication complex in a stepwise sucrose gradient, in which the viral replicase is associated with the smooth cytoplasmic membrane fraction, does not remove the terminal transferase. -
Abstract Book (Pdf)
6th EMBO/EMBL Conference on Science and Society Science and Security 28 – 29 October 2005 at the European Molecular Biology Laboratory Heidelberg, Germany Organising Committee: Andrew Moore (EMBO, Chair), Halldòr Stefànsson (EMBL), Alessandra Bendiscioli (EMBO), Frank Gannon (EMBO), Iain Mattaj (EMBL) Welcome message n September this year, plans for a new bio-defence laboratory in Montana, USA, were Iunveiled. In the $66.5 million facility, researchers will apply similar scientific knowledge to that which makes bio-terrorism or biological warfare a possibility in the first place. The double-edged sword of science application can hardly be more evident. How successfully can we prevent the misuse of research findings that otherwise give us important insights into the workings of nature and prospects of useful applications? What would be the consequences of tackling this problem by constraining research, the mobility of researchers and the funding and publication of their research? Could we, indeed, ever successfully define “research that should not be done”? How much thought should scientists give to the downstream consequences of their work when deciding what to research, or which experiments to do? In June this year, the USA announced that it would delay the introduction of compulsory biometric passports for travellers from 27 countries in Europe and the Asia-Pacific region until October 2006. But whenever they appear, biometric passports will be part of normal life in the future. In the era of international terrorism, this could, indeed, lead to a safer world; an example of a beneficial use of science. On the other hand, it increases the perception by normal citizens that they are being unnecessarily “watched” by an all- seeing, all-controlling state – the so-called Big Brother of Orwell’s 1984. -
THE ROLE of the HERPES SIMPLEX VIRUS TYPE 1 UL28 PROTEIN in TERMINASE COMPLEX ASSEMBLY and FUNCTION by Jason Don Heming Bachelor
THE ROLE OF THE HERPES SIMPLEX VIRUS TYPE 1 UL28 PROTEIN IN TERMINASE COMPLEX ASSEMBLY AND FUNCTION by Jason Don Heming Bachelor of Science, Clarion University of Pennsylvania, 2004 Submitted to the Graduate Faculty of the School of Medicine in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Pittsburgh 2013 UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE This dissertation was presented by Jason Don Heming It was defended on April 18, 2013 and approved by Michael Cascio, Associate Professor, Bayer School of Natural and Environmental Sciences James Conway, Associate Professor, Department of Structural Biology Neal DeLuca, Professor, Department of Microbiology and Molecular Genetics Saleem Khan, Professor, Department of Microbiology and Molecular Genetics Dissertation Advisor: Fred Homa, Associate Professor, Department of Microbiology and Molecular Genetics ii Copyright © by Jason Don Heming 2013 iii THE ROLE OF THE HERPES SIMPLEX VIRUS TYPE 1 UL28 PROTEIN IN TERMINASE COMPLEX ASSEMBLY AND FUNCTION Jason Don Heming, PhD University of Pittsburgh, 2013 Herpes simplex virus type I (HSV-1) is the causative agent of several pathologies ranging in severity from the common cold sore to life-threatening encephalitic infection. During productive lytic infection, over 80 viral proteins are expressed in a highly regulated manner, resulting in the replication of viral genomes and assembly of progeny virions. Cleavage and packaging of replicated, concatemeric viral DNA into newly assembled capsids is critical to virus proliferation and requires seven viral genes: UL6, UL15, UL17, UL25, UL28, UL32, and UL33. Analogy with the well-characterized cleavage and packaging systems of double-stranded DNA bacteriophage suggests that HSV-1 encodes for a viral terminase complex to perform these essential functions, and several studies have indicated that this complex consists of the viral UL15, UL28, and UL33 proteins. -
Inhibition of HIV-1 by an Anti-Integrase Single-Chain Variable
Gene Therapy (1999) 6, 660–666 1999 Stockton Press All rights reserved 0969-7128/99 $12.00 http://www.stockton-press.co.uk/gt Inhibition of HIV-1 by an anti-integrase single-chain variable fragment (SFv): delivery by SV40 provides durable protection against HIV-1 and does not require selection M BouHamdan1, L-X Duan1, RJ Pomerantz1 and DS Strayer1,2 1The Dorrance H Hamilton Laboratories, Center for Human Virology, Division of Infectious Diseases, Department of Medicine; and 2Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA Human immunodeficiency virus type I (HIV-1) encodes the SFv-IN was confirmed by Western blotting and several proteins that are packaged into virus particles. Inte- immunofluorescence staining, which showed that Ͼ90% of grase (IN) is an essential retroviral enzyme, which has SupT1 T-lymphocytic cells treated with SV(Aw) expressed been a target for developing agents to inhibit virus repli- the SFv-IN protein without selection. When challenged, cation. In previous studies, we showed that intracellular HIV-1 replication, as measured by HIV-1 p24 antigen expression of single-chain variable antibody fragments expression and syncytium formation, was potently inhibited (SFvs) that bind IN, delivered via retroviral expression vec- in cells expressing SV40-delivered SFv-IN. Levels of inhi- tors, provided resistance to productive HIV-1 infection in bition of HIV-1 infection achieved using this approach were T-lymphocytic cells. In the current studies, we evaluated comparable to those achieved using murine leukemia virus simian-virus 40 (SV40) as a delivery vehicle for anti-IN (MLV) as a transduction vector, the major difference being therapy of HIV-1 infection. -
Herpes Simplex Virus 1 ICP8 Mutant Lacking Annealing Activity Is Deficient for Viral DNA Replication
Herpes simplex virus 1 ICP8 mutant lacking annealing activity is deficient for viral DNA replication Savithri Weerasooriyaa,1, Katherine A. DiScipioa,b,1, Anthar S. Darwisha,b, Ping Baia, and Sandra K. Wellera,2 aDepartment of Molecular Biology and Biophysics, University of Connecticut School of Medicine, Farmington, CT 06030; and bMolecular Biology and Biochemistry Graduate Program, University of Connecticut School of Medicine, Farmington, CT 06030 Edited by Jack D. Griffith, University of North Carolina, Chapel Hill, NC, and approved December 4, 2018 (received for review October 13, 2018) Most DNA viruses that use recombination-dependent mechanisms culating in patient populations (18–22). Additionally, it has long to replicate their DNA encode a single-strand annealing protein been recognized that viral replication intermediates are com- (SSAP). The herpes simplex virus (HSV) single-strand DNA binding posed of complex X- and Y-branched structures as evidenced by protein (SSB), ICP8, is the central player in all stages of DNA electron microscopy (10, 16) and pulsed-field gel electrophoresis replication. ICP8 is a classical replicative SSB and interacts physi- (15, 23, 24). ′ ′ cally and/or functionally with the other viral replication proteins. The HSV exo/SSAP, composed of a 5 -to-3 exonuclease Additionally, ICP8 can promote efficient annealing of complemen- (UL12) and an SSAP (ICP8), is capable of promoting strand ex- tary ssDNA and is thus considered to be a member of the SSAP change in vitro (25, 26). More recently, we have shown that HSV infection stimulates single-strand annealing (27), and ICP8 has family. The role of annealing during HSV infection has been been reported to promote recombineering in transfected cells difficult to assess in part, because it has not been possible to (28). -
“Let There Be Life”
Focus: Brave New World “We have reason to believe that the disease is created by a man-made super pathogen...” AND MAN SAID, “LETa short story THERE BE LIFE” By Lawrence Valverde e have reason to believe the nearly 200 scientists simmered with “Wdisease is caused by a man- mumbled comments. The researcher made super-pathogen. The construc- whose speech had been interrupted tion seems to be loosely based on the straightened himself and raised his smallpox virus, but with significant voice in response. modifications, including genes encod- “I hear your concern, Dr. Boots, ing immune system antagonists. It but we have not confirmed whether or also seems to have been specifically not this is, in fact, a terrorist act…” engineered to resist known antivi- “Who else would do such a thing, ral…” Dr. Cervantes?” Dr. Boots demanded. “What do you mean specifically “It wasn’t necessarily done on engineered!” boomed an overweight purpose…” said Dr. Cervantes—the man as he hauled himself out of speaker—but he was interrupted by his chair. “Are you proposing that the clamor that erupted as scientists terrorists may have the technology jump up from their seats. Dr. Cervantes to synthetically create their own vi- frowned. Trying to speak over the ruses?” The surrounding panel of crowd was clearly a lost cause. When credit: Clipart courtesy FCIT. http://etc.usf.edu/clipart credit: Clipart courtesy FCIT. fall 2008 • Harvard Science Review 9 valverde.indd 9 2/9/2009 11:24:54 PM Focus: Brave New World did this whole business with artificially Dr. Boots sputtered. -
Type of the Paper (Article
Viruses 2018 – Breakthroughs in Viral Replication Faculty of Biology University of Barcelona Spain 7 – 9 February 2018 Conference Chair Eric O. Freed Conference Co-Chair Albert Bosch Organised by Conference Secretariat Antonio Peteira Man Luo George Andrianou Nikoleta Kiapidou Kristjana Xhuxhi Pablo Velázquez Lucia Russo Sara Martínez Lynn Huang Sarai Rodríguez Viruses 2018 – Breakthroughs in Viral Replication 1 CONTENTS Abridged Programme 5 Conference Programme 6 Welcome 13 General Information 15 Abstracts – Session 1 25 General Topics in Virology Abstracts – Session 2 45 Structural Virology Abstracts – Session 3 67 Virus Replication Compartments Abstracts – Session 4 89 Replication and Pathogenesis of RNA viruses Abstracts – Session 5 105 Genome Packaging and Replication/Assembly Abstracts – Session 6 127 Antiviral Innate Immunity and Viral Pathogenesis Abstracts – Poster Exhibition 147 List of Participants 297 Viruses 2018 – Breakthroughs in Viral Replication 3 Viruses 2018 – Breakthroughs in Viral Replication 7 – 9 February 2018, Barcelona, Spain Wednesday Thursday Friday 7 February 2018 8 February 2018 9 February 2018 S3. Virus S5. Genome Check-in Replication Packaging and Compartments Replication/Assembly Opening Ceremony S1. General Topics in Virology Morning Coffee Break S1. General Topics S3. Virus S5. Genome in Virology Replication Packaging and Compartments Replication/Assembly Lunch S2. Structural S4. Replication and S6. Antiviral Innate Virology Pathogenesis of Immunity and Viral RNA Viruses Pathogenesis Coffee Break Apéro and Poster Coffee Break Session S2. Structural S6. Antiviral Innate Virology Immunity and Viral Afternoon Conference Group Pathogenesis Photograph Closing Remarks Conference Dinner Wednesday 7 February 2018: 08:00 - 12:30 / 14:00 - 18:00 / Conference Dinner: 20:30 Thursday 8 February 2018: 08:30 - 12:30 / 14:00 - 18:30 Friday 9 February 2018: 08:30 - 12:30 / 14:00 - 18:15 Viruses 2018 – Breakthroughs in Viral Replication 5 Conference Programme Wednesday 7 February 08:00 – 08:45 Check-in 08:45 – 09:00 Opening Ceremony by Eric O. -
Hepatitis B Virus X Protein Inhibits P53 Sequence-Specific DNA Binding
Proc. Nati. Acad. Sci. USA Vol. 91, pp. 2230-2234, March 1994 Medical Sciences Hepatitis B virus X protein inhibits p53 sequence-specific DNA binding, transcriptional activity, and association with transcription factor ERCC3 XIN WEI WANG*, KATHLEEN FORRESTER*, HEIDI YEH*, MARK A. FEITELSONt, JEN-REN GUI, AND CURTIS C. HARRIS*§ *Laboratory of Human Carcinogenesis, Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; tDepartment of Pathology and Cell Biology, Jefferson Medical College, Philadelphia, PA 19107; and tDepartment of Molecular Biology and Biochemistry, Shanghai Cancer Institute, Shanghai, People's Republic of China. Communicated by Bert Vogelstein, December 27, 1993 (receivedfor review December 9, 1993) ABSTRACT Chronic active hepatitis caused by infection about the role of HBX in HCC development. In this report, with hepatitis B virus, a DNA virus, is a major risk factor for we present results consistent with the hypothesis that HBX human hepatocellular carcinoma. Since the oncogenicity of binds to p53 and abrogates its normal cellular functions. several DNA viruses is dependent on the interaction of their viral oncoproteins with cellular tumor-suppressor gene prod- MATERIAL AND METHODS ucts, we investigated the interaction between hepatitis B virus X protein (HBX) and human wild-type p53 protein. HBX Plasmids. Plasmid constructs encoding GST-p53-WT, con- complexes with the wild-type p53 protein and inhibits its taining glutathione S-transferase (GST) fused to human wild- sequence-specific DNA binding in vitro. HBX expresslin also type p53, and GST-p53-135Y, containing GST fused to the inhibits p53-mediated transcrptional activation in vivo and the mutant p53 containing a His -* Tyr mutation at codon 135, in vitro asoition of p53 and ERCC3, a general transcription were provided by Jon Huibregtse (National Cancer Institute) factor involved in nucleotide excision repair. -
An Exploration of the Interplay Between HSV-1 and the Non-Homologous End Joining Proteins PAXX and DNA-Pkcs
An exploration of the interplay between HSV-1 and the non-homologous end joining proteins PAXX and DNA-PKcs Benjamin James Trigg Gonville and Caius College This dissertation is submitted for the degree of Doctor of Philosophy September 2017 2. Abstract An exploration of the interplay between HSV-1 and the non-homologous end joining proteins PAXX and DNA-PKcs Benjamin James Trigg Abstract DNA damage response (DDR) pathways are essential in maintaining genomic integrity in cells, but many DDR proteins have other important functions such as in the innate immune sensing of cytoplasmic DNA. Some DDR proteins are known to be beneficial or restrictive to viral infection, but most remain uncharacterised in this respect. Non-homologous end joining (NHEJ) is a mechanism of double stranded DNA (dsDNA) repair that functions to rapidly mend broken DNA ends. The NHEJ machinery is well characterised in the context of DDR but recent studies have linked the same proteins to innate immune DNA sensing and, hence, anti-viral responses. The aim of this thesis is to further investigate the interplay between herpes simplex virus 1 (HSV-1), a dsDNA virus, and two NHEJ proteins, DNA protein kinase catalytic subunit (DNA- PKcs) and paralogue of XRCC4 and XLF (PAXX). PAXX was first described in the literature as a NHEJ protein in 2015, but whether it has any role in the regulation of virus infection has not been established. Here we show that PAXX acts as a restriction factor for HSV-1 because PAXX-/- (KO) cells produce a consistently higher titre of HSV-1 than the respective wild type (WT) cells.