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Entwicklung Einer Software Zur Identifizierung Neuartiger Und
Entwicklung einer Software zur Identifizierung neuartiger und bekannter Infektionserreger in klinischen Proben Dissertation zur Erlangung des Doktorgrades an der Fakult¨at fur¨ Mathematik, Informatik und Naturwissenschaften Fachbereich Biologie der Universit¨at Hamburg vorgelegt von Malik Alawi Hamburg, 2020 Vorsitzender der Prufungskommission¨ Dr. PD Andreas Pommerening-R¨oser Gutachter Professor Dr. Adam Grundhoff Professor Dr. Stefan Kurtz Datum der Disputation 30. April 2021 Abstract Sequencing of diagnostic samples is widely considered a key technology that may fun- damentally improve infectious disease diagnostics. The approach can not only identify pathogens already known to cause a specific disease, but may also detect pathogens that have not been previously attributed to this disease, as well as completely new, previously unknown pathogens. Therefore, it may significantly increase the level of preparedness for future outbreaks of emerging pathogens. This study describes the development and application of methods for the identification of pathogenic agents in diagnostic samples. The methods have been successfully applied multiple times under clinical conditions. The corresponding results have been published within the scope of this thesis. Finally, the methods were made available to the scientific community as an open source bioinformatics tool. The novel software was validated by conventional diagnostic methods and it was compared to established analysis pipelines using authentic clinical samples. It is able to identify pathogens from different diagnostic entities and often classifies viral agents down to strain level. Furthermore, the method is capable of assembling complete viral genomes, even from samples containing multiple closely related viral strains of the same viral family. In addition to an improved method for taxonomic classification, the software offers functionality which is not present in established analysis pipelines. -
Rice Scholarship Home
RICE UNIVERSITY By A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE APPROVED, THESIS COMMITTEE HOUSTON, TEXAS ABSTRACT Data-driven modeling to infer the function of viral replication in a counting-based decision by Seth Coleman Cells use gene regulatory networks, sets of genes connected through a web of bio- chemical interactions, to select a developmental pathway based on signals from their environment. These processes, called cell-fate decisions, are ubiquitous in biology. Yet efforts to study cell-fate decisions are often stymied by the inherent complexity of organisms. Simple model systems provide attractive alternative platforms to study cell-fate decisions and gain insights which may be broadly applicable. Infection of E. coli by the virus lambda is one such model system. The outcome of this viral infection is dependent on the number of initially coinfecting viruses (multiplicity of infection, or MOI), which the viral regulatory network appears to `count'. Yet precisely how the viral regulatory network responds to MOI is still unclear, as is how the system is able to achieve sensitivity to MOI despite viral replication, which quickly obfuscates initial viral copy number. In this thesis, I used mathematical modeling of the network dynamics, calibrated by experimental measurements of viral replication and gene ex- pression during infection, to demonstrate how the network responds to MOI and to show that viral replication actually facilitates, rather than hinders, a counting-based decision. This work provides an example of how complex behaviors can emerge from the interplay between gene/network copy number and gene expression, whose coupling iii cannot be ignored in developing a predictive description of cellular decision-making. -
The Virus Social
editorial Welcome to the virus social Long-known to happen in other realms of the microscopic and macroscopic worlds, social interactions in viruses are increasingly being appreciated and have the potential to infuence many processes, including viral pathogenesis, resistance to antiviral immunity, establishment of persistence and even life cycle choice. ngoing efforts to characterise show that the ability of a vesicular stomatitis communication system to determine the virosphere have identified virus to suppress interferon (IFN)-mediated the number of recent infections in the Oviruses in every environment innate immunity is a social altruistic trait population by measuring the level of a studied, infecting every life form and even that, though costly for the viruses that phage-encoded peptide, and switch to a parasitizing other viruses. In addition to carry it and produce less progeny in the lysogenic lifestyle to prevent killing off their this vast viral diversity, variants frequently short term, enables the replication of other host when the amount of peptide increases emerge within populations of a given virus members of the viral population that do not over a certain threshold5. Cooperation also through mutation, deletion, recombination repress IFN (ref. 2). The demonstration that allows phage populations to resist bacterial or reassortment. Co-circulation of different social evolution rules govern viral innate CRISPR-mediated immune defence; initial viruses in the same areas of the world, immune evasion and virulence provides phage resistance may not be sufficient to sharing hosts and vectors, increases the a framework for future study of viral overcome the immune response, but creates chances of co-infection and co-transmission social traits. -
Changes to Virus Taxonomy 2004
Arch Virol (2005) 150: 189–198 DOI 10.1007/s00705-004-0429-1 Changes to virus taxonomy 2004 M. A. Mayo (ICTV Secretary) Scottish Crop Research Institute, Invergowrie, Dundee, U.K. Received July 30, 2004; accepted September 25, 2004 Published online November 10, 2004 c Springer-Verlag 2004 This note presents a compilation of recent changes to virus taxonomy decided by voting by the ICTV membership following recommendations from the ICTV Executive Committee. The changes are presented in the Table as decisions promoted by the Subcommittees of the EC and are grouped according to the major hosts of the viruses involved. These new taxa will be presented in more detail in the 8th ICTV Report scheduled to be published near the end of 2004 (Fauquet et al., 2004). Fauquet, C.M., Mayo, M.A., Maniloff, J., Desselberger, U., and Ball, L.A. (eds) (2004). Virus Taxonomy, VIIIth Report of the ICTV. Elsevier/Academic Press, London, pp. 1258. Recent changes to virus taxonomy Viruses of vertebrates Family Arenaviridae • Designate Cupixi virus as a species in the genus Arenavirus • Designate Bear Canyon virus as a species in the genus Arenavirus • Designate Allpahuayo virus as a species in the genus Arenavirus Family Birnaviridae • Assign Blotched snakehead virus as an unassigned species in family Birnaviridae Family Circoviridae • Create a new genus (Anellovirus) with Torque teno virus as type species Family Coronaviridae • Recognize a new species Severe acute respiratory syndrome coronavirus in the genus Coro- navirus, family Coronaviridae, order Nidovirales -
P1 Bacteriophage and Tol System Mutants
P1 BACTERIOPHAGE AND TOL SYSTEM MUTANTS Cari L. Smerk A Thesis Submitted to the Graduate College of Bowling Green State University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE August 2007 Committee: Ray A. Larsen, Advisor Tami C. Steveson Paul A. Moore Lee A. Meserve ii ABSTRACT Dr. Ray A. Larsen, Advisor The integrity of the outer membrane of Gram negative bacteria is dependent upon proteins of the Tol system, which transduce cytoplasmic-membrane derived energy to as yet unidentified outer membrane targets (Vianney et al., 1996). Mutations affecting the Tol system of Escherichia coli render the cells resistant to a bacteriophage called P1 by blocking the phage maturation process in some way. This does not involve outer membrane interactions, as a mutant in the energy transucer (TolA) retained wild type levels of phage sensitivity. Conversely, mutations affecting the energy harvesting complex component, TolQ, were resistant to lysis by bacteriophage P1. Further characterization of specific Tol system mutants suggested that phage maturation was not coupled to energy transduction, nor to infection of the cells by the phage. Quantification of the number of phage produced by strains lacking this protein also suggests that the maturation of P1 phage requires conditions influenced by TolQ. This study aims to identify the role that the TolQ protein plays in the phage maturation process. Strains of cells were inoculated with bacteriophage P1 and the resulting production by the phage of viable progeny were determined using one step growth curves (Ellis and Delbruck, 1938). Strains that were lacking the TolQ protein rendered P1 unable to produce the characteristic burst of progeny phage after a single generation of phage. -
(12) United States Patent (10) Patent No.: US 9,096,585 B2 Shaw Et Al
US009096585B2 (12) United States Patent (10) Patent No.: US 9,096,585 B2 Shaw et al. (45) Date of Patent: Aug. 4, 2015 (54) ANTIVIRAL COMPOUNDS AND USES (2013.01); C07D 413/10 (2013.01); C07D THEREOF 413/12 (2013.01); A61 K 3 1/5377 (2013.01); A61 K3I/55 (2013.01) (75) Inventors: Megan Shaw, New York, NY (US); (58) Field of Classification Search Hans-Heinrich Hoffmann, New York, CPC. A61K 31/4245; A61K31/5377; A61K31/55 NY (US); Adolfo Garcia-Sastre, New USPC .................................... 514/364, 217.1, 236.2 York, NY (US); Peter Palese, Leonia, NJ See application file for complete search history. US (US) (56) References Cited (73) Assignee: Icahn School of Medicine at Mount Sinai, New York, NY (US) U.S. PATENT DOCUMENTS 6,384,064 B2 5, 2002 Camden (*) Notice: Subject to any disclaimer, the term of this 8,278,342 B2 10/2012 Ricciardi patent is extended or adjusted under 35 Continued U.S.C. 154(b) by 210 days. (Continued) (21) Appl. No.: 13? 700,049 FOREIGN PATENT DOCUMENTS y x- - - 9 (22) PCT Filed1C Mavay 31,51, 2011 WO WO 2009,136979 A2 11/2009 OTHER PUBLICATIONS (86). PCT No.: PCT/US2011/038515 Chu et al. "Analysis of the endocytic pathway mediating the infec S371 (c)(1), tious entry of mosquito-borne flavivirus West Nile into Aedes (2), (4) Date: Feb. 14, 2013 albopictus mosquito (C6/36) cells.” Virology, 2006, vol. 349, pp. 463-475. (87) PCT Pub. No.: WO2011/150413 (Continued) PCT Pub. Date: Dec. 1, 2011 Primary Examiner — Shengjun Wang (65) Prior Publication Data (74) Attorney, Agent, or Firm — Jones Day US 2013/O137678A1 May 30, 2013 (57) ABSTRACT O O Described herein are Compounds, compositions comprising Related U.S. -
Genomes of the T4-Related Bacteriophages As Windows on Microbial Genome Evolution
Petrov et al. Virology Journal 2010, 7:292 http://www.virologyj.com/content/7/1/292 REVIEW Open Access Genomes of the T4-related bacteriophages as windows on microbial genome evolution Vasiliy M Petrov1, Swarnamala Ratnayaka1, James M Nolan2, Eric S Miller3, Jim D Karam1* Abstract The T4-related bacteriophages are a group of bacterial viruses that share morphological similarities and genetic homologies with the well-studied Escherichia coli phage T4, but that diverge from T4 and each other by a number of genetically determined characteristics including the bacterial hosts they infect, the sizes of their linear double- stranded (ds) DNA genomes and the predicted compositions of their proteomes. The genomes of about 40 of these phages have been sequenced and annotated over the last several years and are compared here in the con- text of the factors that have determined their diversity and the diversity of other microbial genomes in evolution. The genomes of the T4 relatives analyzed so far range in size between ~160,000 and ~250,000 base pairs (bp) and are mosaics of one another, consisting of clusters of homology between them that are interspersed with segments that vary considerably in genetic composition between the different phage lineages. Based on the known biologi- cal and biochemical properties of phage T4 and the proteins encoded by the T4 genome, the T4 relatives reviewed here are predicted to share a genetic core, or “Core Genome” that determines the structural design of their dsDNA chromosomes, their distinctive morphology and the process of their assembly into infectious agents (phage morphogenesis). -
Multiple Origins of Prokaryotic and Eukaryotic Single-Stranded DNA Viruses from Bacterial and Archaeal Plasmids
ARTICLE https://doi.org/10.1038/s41467-019-11433-0 OPEN Multiple origins of prokaryotic and eukaryotic single-stranded DNA viruses from bacterial and archaeal plasmids Darius Kazlauskas 1, Arvind Varsani 2,3, Eugene V. Koonin 4 & Mart Krupovic 5 Single-stranded (ss) DNA viruses are a major component of the earth virome. In particular, the circular, Rep-encoding ssDNA (CRESS-DNA) viruses show high diversity and abundance 1234567890():,; in various habitats. By combining sequence similarity network and phylogenetic analyses of the replication proteins (Rep) belonging to the HUH endonuclease superfamily, we show that the replication machinery of the CRESS-DNA viruses evolved, on three independent occa- sions, from the Reps of bacterial rolling circle-replicating plasmids. The CRESS-DNA viruses emerged via recombination between such plasmids and cDNA copies of capsid genes of eukaryotic positive-sense RNA viruses. Similarly, the rep genes of prokaryotic DNA viruses appear to have evolved from HUH endonuclease genes of various bacterial and archaeal plasmids. Our findings also suggest that eukaryotic polyomaviruses and papillomaviruses with dsDNA genomes have evolved via parvoviruses from CRESS-DNA viruses. Collectively, our results shed light on the complex evolutionary history of a major class of viruses revealing its polyphyletic origins. 1 Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio av. 7, Vilnius 10257, Lithuania. 2 The Biodesign Center for Fundamental and Applied Microbiomics, School of Life Sciences, Center for Evolution and Medicine, Arizona State University, Tempe, AZ 85287, USA. 3 Structural Biology Research Unit, Department of Integrative Biomedical Sciences, University of Cape Town, Rondebosch, 7700 Cape Town, South Africa. -
Beyond Arbitrium: Identification of a Second Communication System In
Beyond arbitrium: identification of a second communication system in Bacillus phage phi3T that may regulate host defense mechanisms Charles Bernard, Yanyan Li, Philippe Lopez, Eric Bapteste To cite this version: Charles Bernard, Yanyan Li, Philippe Lopez, Eric Bapteste. Beyond arbitrium: identification of a second communication system in Bacillus phage phi3T that may regulate host defense mechanisms. ISME Journal, Nature Publishing Group, 2020, 10.1038/s41396-020-00795-9. hal-03028148 HAL Id: hal-03028148 https://hal.archives-ouvertes.fr/hal-03028148 Submitted on 27 Nov 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. The ISME Journal https://doi.org/10.1038/s41396-020-00795-9 ARTICLE Beyond arbitrium: identification of a second communication system in Bacillus phage phi3T that may regulate host defense mechanisms 1,2 2 1 1 Charles Bernard ● Yanyan Li ● Philippe Lopez ● Eric Bapteste Received: 2 April 2020 / Revised: 17 September 2020 / Accepted: 24 September 2020 © The Author(s) 2020. This article is published with open access Abstract The evolutionary stability of temperate bacteriophages at low abundance of susceptible bacterial hosts lies in the trade-off between the maximization of phage replication, performed by the host-destructive lytic cycle, and the protection of the phage-host collective, enacted by lysogeny. -
Genetic Content and Evolution of Adenoviruses Andrew J
Journal of General Virology (2003), 84, 2895–2908 DOI 10.1099/vir.0.19497-0 Review Genetic content and evolution of adenoviruses Andrew J. Davison,1 Ma´ria Benko´´ 2 and Bala´zs Harrach2 Correspondence 1MRC Virology Unit, Institute of Virology, Church Street, Glasgow G11 5JR, UK Andrew Davison 2Veterinary Medical Research Institute, Hungarian Academy of Sciences, H-1581 Budapest, [email protected] Hungary This review provides an update of the genetic content, phylogeny and evolution of the family Adenoviridae. An appraisal of the condition of adenovirus genomics highlights the need to ensure that public sequence information is interpreted accurately. To this end, all complete genome sequences available have been reannotated. Adenoviruses fall into four recognized genera, plus possibly a fifth, which have apparently evolved with their vertebrate hosts, but have also engaged in a number of interspecies transmission events. Genes inherited by all modern adenoviruses from their common ancestor are located centrally in the genome and are involved in replication and packaging of viral DNA and formation and structure of the virion. Additional niche-specific genes have accumulated in each lineage, mostly near the genome termini. Capture and duplication of genes in the setting of a ‘leader–exon structure’, which results from widespread use of splicing, appear to have been central to adenovirus evolution. The antiquity of the pre-vertebrate lineages that ultimately gave rise to the Adenoviridae is illustrated by morphological similarities between adenoviruses and bacteriophages, and by use of a protein-primed DNA replication strategy by adenoviruses, certain bacteria and bacteriophages, and linear plasmids of fungi and plants. -
On the Stability of Sequences Inserted Into Viral Genomes Anouk Willemsen1,*,† and Mark P
Virus Evolution, 2019, 5(2): vez045 doi: 10.1093/ve/vez045 Review article On the stability of sequences inserted into viral genomes Anouk Willemsen1,*,† and Mark P. Zwart2,*,‡ 1Laboratory MIVEGEC (UMR CNRS IRD University of Montpellier), Centre National de la Recherche Scientifique (CNRS), 911 Avenue Agropolis, BP 64501, 34394 Montpellier cedex 5, France and 2Netherlands Institute of Ecology (NIOO-KNAW), Postbus 50, 6700 AB, Wageningen, The Netherlands *Corresponding author: E-mail: [email protected]; [email protected] †http://orcid.org/0000-0002-8511-3244 ‡http://orcid.org/0000-0003-4361-7636 Abstract Viruses are widely used as vectors for heterologous gene expression in cultured cells or natural hosts, and therefore a large num- ber of viruses with exogenous sequences inserted into their genomes have been engineered. Many of these engineered viruses are viable and express heterologous proteins at high levels, but the inserted sequences often prove to be unstable over time and are rapidly lost, limiting heterologous protein expression. Although virologists are aware that inserted sequences can be unstable, processes leading to insert instability are rarely considered from an evolutionary perspective. Here, we review experimental work on the stability of inserted sequences over a broad range of viruses, and we present some theoretical considerations concerning insert stability. Different virus genome organizations strongly impact insert stability, and factors such as the position of insertion can have a strong effect. In addition, we argue that insert stability not only depends on the characteristics of a particular genome, but that it will also depend on the host environment and the demography of a virus population. -
The Viruses of Wild Pigeon Droppings
The Viruses of Wild Pigeon Droppings Tung Gia Phan1,2, Nguyen Phung Vo1,3,A´ kos Boros4,Pe´ter Pankovics4,Ga´bor Reuter4, Olive T. W. Li6, Chunling Wang5, Xutao Deng1, Leo L. M. Poon6, Eric Delwart1,2* 1 Blood Systems Research Institute, San Francisco, California, United States of America, 2 Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, United States of America, 3 Pharmacology Department, School of Pharmacy, Ho Chi Minh City University of Medicine and Pharmacy, Ho Chi Minh, Vietnam, 4 Regional Laboratory of Virology, National Reference Laboratory of Gastroenteric Viruses, A´ NTSZ Regional Institute of State Public Health Service, Pe´cs, Hungary, 5 Stanford Genome Technology Center, Stanford, California, United States of America, 6 Centre of Influenza Research and School of Public Health, University of Hong Kong, Hong Kong SAR Abstract Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses.