DOCSLIB.ORG

Profile of Eckard Wimmer

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Profile of Eckard Wimmer PROFILE Profile of Eckard Wimmer he finding caused an uproar. vitalism—the belief that chemicals in liv- Researchers at Stony Brook Uni- ing systems are somehow distinct from Tversity in New York had engi- the chemicals in inorganic systems, such neered poliovirus in a test tube as salt and rocks. That notion was shat- (1). The discovery, led by Eckard Wimmer, tered in 1828, when German chemist elected in 2012 to the National Academy Friedrich Wöhler synthesized the organic of Sciences, dispelled the belief that compound urea from inorganic pre- viruses require a live host to grow cursors (5). and spread. By the 1940s, theoretical physicists and The thought of synthetic viruses terrified biochemists had begun to wonder about an American public still reeling from 9/11 what constitutes life. Wimmer was en- and the subsequent anthrax attacks. What thralled. Biochemistry squared perfectly if the technology to engineer viruses with his worldview, the idea that something wound up in the hands of bioterrorists? as seemingly profound as life could be pared However, today, just a decade later, it is down to its simplest—chemical—form. widely accepted that the ability to engineer While completing his second post- viruses also allows researchers to develop doctoral fellowship at the University of viruses that work as synthetic vaccines, British Columbia in Vancouver in the to carry genetic material into a cell for use mid-1960s, Wimmer attended a talk on in gene therapies, or to preferentially viruses and had his eureka moment. “It attack cancer cells (2). was clear, even though it wasn’t men- Wimmer says his motivations for engi- tioned in that talk, that if viruses can be neering polio were strictly scientific. crystallized just like chemicals, it must be Wimmer had solved the code—or genome possible to describe their components, the sequence—for polio in 1981, but his goal, virions, with an empirical formula,” he “ he says, was to boot the synthesized ge- Eckard Wimmer. says (6). At that conference, Wimmer ” nome for it to become a virus. The discussed the idea with Elias Reichmann, boot worked. a plant virologist at the University of Il- Few realized that Wimmer had done munist regime that had taken root in East linois in Urbana–Champaign. Reichmann fl something extraordinary for science and Germany. The family ed again, ulti- asked Wimmer to join his laboratory. society. Viruses, Wimmer and others have mately becoming refugees in what was “Now I was stuck and had to work on long believed, hold a unique place in bi- then West Germany. Through so much viruses,” Wimmer jokes. ology: Outside the body, they behave like dislocation, Wimmer says, “the family lost chemicals, but, once inside, they propagate its roots.” Adopting Polio “ in true Darwinian fashion. Viruses are Wimmer suffered nightmares through- At Reichmann’s laboratory, Wimmer ” chemicals with a life cycle, Wimmer says. out his teen years and long thereafter. initially worked with plant viruses, his “ Once they get into living cells, they begin Forced to question the senselessness of mentor’s specialty (7–9). However, that to replicate, following the laws of heredity human strife early on, Wimmer emerged topic of study proved time-consuming, as ” and genetic variation. Put another way, from his childhood an avowed atheist. both plants and their viruses are generally “ viruses hover on the boundary between life Every child who has been exposed to slow-growing. A colleague suggested that and nonlife. warfare or lives in an area with warfare ’ ... ” Wimmer take a look at poliovirus, which Wimmer s Inaugural Article brings him carries a burden for his whole life, was fast-growing. “Poliovirus fulfilled all one step closer to pinning down the inner Wimmer says. my expectations,” Wimmer says. “You workings of poliovirus (3). In this case, The desire to understand life via sci- could grow it in six hours.” Song et al. looked for the parts of the ence, not some higher power, would ul- — ’ In 1968, Wimmer became an assistant polio genome that make it so deadly that timately become integral to Wimmer s professor in the microbiology department is, the parts of the code that allow the virus later career. Wimmer chose to study at Saint Louis University in Missouri. to replicate and kill host cells. The re- chemistry in large part because his father fi There, Wimmer found himself in an empty searchers found two hidden signals: nu- studied chemistry. After nishing his un- laboratory with almost no funding. And cleotide sequences dubbed α and β. dergraduate degree in chemistry at the yet, he recalls, “I was professionally in- University of Rostock in Germany in dependent for the first time in my life and War Child 1956, Wimmer went to the University of in control of my career. I felt like a king.” Wimmer’s interest in science coincided Göttingen in Germany for graduate His first grant application to sequence the with growing doubts about his Protestant school. There he began his earliest work polio genome was roundly rejected, as no upbringing. Born in Berlin in 1936, in structural analysis and synthesis of one thought it could be done. Then, in Wimmer survived tragedy and war early natural compounds. His task was finding 1969, Wimmer was invited to spend six in life. His father died when Wimmer was the structure of rhodomycinons (4), months working with David Baltimore, just three years old. By then, Hitler a class of compounds whose derivatives a biologist then at the Massachusetts In- had begun his march across Europe. have antitumor activities. Wimmer’s mother whisked him and his During his postdoctoral work in the stitute of Technology in Cambridge, MA. two older brothers to her parents’ place in early 1960s, also at Göttingen, Wimmer Baltimore taught Wimmer the ins and outs Saxony, where the family largely escaped enrolled in a course in microbiology. the violence. In Saxony, however, Wim- There he heard about biochemistry, then fi ’ fl fi This is a Pro le of a recently elected member of the mer s grandfather was labeled a capitalist, a edgling eld in Germany. Bio- National Academy of Sciences to accompany the member’s a term that was anathema to the com- chemistry arose out of the ashes of Inaugural Article on page 14301 in issue 36 of volume 109. www.pnas.org/cgi/doi/10.1073/pnas.1221558110 PNAS | February 5, 2013 | vol. 110 | no. 6 | 1973–1975 of polio research (10). Eventually, Wimmer face of a cell. Once inside the cell, the virus liovirus in a test tube, he also faced in- was able to achieve the goals postulated releases its large genome, programmed to tense criticism, even ridicule. However, in his original grant application. make more of itself. Wimmer wanted to the technology to invent viruses already In the mid-1970s, Wimmer moved to find the cellular receptor that polio sub- existed, Wimmer says. All he did was put New York to help start the microbiology verts, so he inserted human genes into it to the test. Several years later, Wim- department at the then-new state school mouse cells to make them susceptible to mer published an essay in the journal at Stony Brook. He has remained there polio (mice lack a polio receptor and are EMBO Reports reflecting on his 2002 ever since. Soon, Wimmer and his col- thus not susceptible to the disease). Then, publication and the subsequent uproar leagues deciphered poliovirus’ chemical using an antibody, he combed through (25). In it, he acknowledges that creating structure, a finding that provided the millions of mouse cells to find the receptor viruses from scratch does, in theory, ne- foundation for Wimmer’s subsequent it bound to. By cloning those rare mouse gate our ability to eradicate those vi- efforts to map the biological information cells, Wimmer identified the receptor, ruses. He also notes that any eradication hidden in the viral genome, a feat he which now goes by the name CD155 (21). plan must take into account this reality. accomplished in the early 1980s. The re- Subsequent studies revealed that tumor That burden is the consequence of sulting gene map proved for the first time cells overproduce this receptor, revealing progress, he says, of which the synthesis that the poliovirus genome encodes a sin- it to be a good biomarker for cancer (22). of poliovirus is a part. Case in point: gle giant protein, the polyprotein (11–13). Polio has proven so resistant to eradi- Although the presence of such a poly- Launching Life cation that the World Health Organiza- protein had been predicted, Wimmer’s It had been known for decades that tion and other private research work proved its existence (14). He was inserting a purified, or naked, form of the foundations are now funding efforts to also able to identify the parts of the ge- RNA genome of poliovirus into cells could develop new polio vaccines (26). Syn- nome that created the enzymes needed to prompt it to complete its life cycle and thesizing poliovirus, Wimmer continues, cleave the polyprotein (15). produce more virus. However, it took until fits under the National Institutes of the 1990s for Wimmer to realize that he Health “dual use research of concern” Deconstructing Viruses just might be able to create poliovirus designation—that is, situations in which The genome sequence gave Wimmer without cells—or without a live host. In the same technology can be used for a sweeping view of poliovirus. However, 1991, his team mashed human cells and malfeasance or human betterment (27). he didn’t yet know the intricacies of its stripped them of essential elements, in- The ability to create viruses from workings.
Load more

Recommended publications
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • “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.
    [Show full text]
  • Profile of Eckard Wimmer
    PROFILE Profile of Eckard Wimmer he finding caused an uproar. vitalism—the belief that chemicals in liv- Researchers at Stony Brook Uni- ing systems are somehow distinct from Tversity in New York had engi- the chemicals in inorganic systems, such neered poliovirus in a test tube as salt and rocks. That notion was shat- (1). The discovery, led by Eckard Wimmer, tered in 1828, when German chemist elected in 2012 to the National Academy Friedrich Wöhler synthesized the organic of Sciences, dispelled the belief that compound urea from inorganic pre- viruses require a live host to grow cursors (5). and spread. By the 1940s, theoretical physicists and The thought of synthetic viruses terrified biochemists had begun to wonder about an American public still reeling from 9/11 what constitutes life. Wimmer was en- and the subsequent anthrax attacks. What thralled. Biochemistry squared perfectly if the technology to engineer viruses with his worldview, the idea that something wound up in the hands of bioterrorists? as seemingly profound as life could be pared However, today, just a decade later, it is down to its simplest—chemical—form. widely accepted that the ability to engineer While completing his second post- viruses also allows researchers to develop doctoral fellowship at the University of viruses that work as synthetic vaccines, British Columbia in Vancouver in the to carry genetic material into a cell for use mid-1960s, Wimmer attended a talk on in gene therapies, or to preferentially viruses and had his eureka moment. “It attack cancer cells (2). was clear, even though it wasn’t men- Wimmer says his motivations for engi- tioned in that talk, that if viruses can be neering polio were strictly scientific.
    [Show full text]
  • Bert Lawrence Semler
    Curriculum Vitae: Bert Lawrence Semler Contact Information Department of Microbiology and Molecular Genetics School of Medicine, Med Sci B237 University of California Irvine, CA 92697 USA E-mail: [email protected] Phone: (949) 824-7573 FAX: (949) 824-2694 Education 1970-1974 University of California, Irvine Bachelor of Science - Biological Sciences 1974-1979 University of California, San Diego Doctor of Philosophy - Biology Research and Professional Experience 1972-1974 Undergraduate research with Professor H. W. Moore Department of Chemistry, University of California, Irvine 1975-1979 Graduate student with Professor John J. Holland Department of Biology, University of California, San Diego 1979-1983 Postdoctoral fellow with Professor Eckard Wimmer, Department of Microbiology, State University of New York at Stony Brook 1983-1987 Assistant Professor, Department of Microbiology and Molecular Genetics College of Medicine, University of California, Irvine 1987-1991 Associate Professor, Department of Microbiology and Molecular Genetics College of Medicine, University of California, Irvine 1991-2018 Professor, Department of Microbiology and Molecular Genetics School of Medicine, University of California, Irvine 1996-2006 Chair, Department of Microbiology and Molecular Genetics School of Medicine, University of California, Irvine 2000-2010 Associate Director, Center for Virus Research University of California, Irvine 2010-present Director, Center for Virus Research University of California, Irvine 2018-present Distinguished Professor, Department
    [Show full text]
  • NAT265 NEW Mx
    news Poliovirus advance sparks fears of data curbs Erika Check, Washington The recent laboratory synthesis of an infec- tious poliovirus is prompting fears among SCIENCE US biologists that the publication of results GETTY IMAGES deemed potentially useful to terrorists may be restricted. The virus was synthesized by a team led by virologist Eckard Wimmer at the State University of New York at Stony Brook. The results, published online by Science on 11 July (J. Cello, A. V. Paul & E. Wimmer Science 10.1126/science.1072266), sparked media reports worldwide suggesting that similar techniques might be used by terrorists to synthesize the Ebola virus or even smallpox. For Eckard Wimmer, his results brought a ‘scary Culture shock: researchers have synthesized this Geneticists fear that the report — the first realization’ that viruses can be recreated. infectious poliovirus in the laboratory. demonstration that a published genome can be turned into an infectious virus — will been used to demonstrate the technique. sequence information. He claims that the encourage calls for a clampdown on the open Wimmer defends his group’s decision to latest research proves that the world can publication of gene sequences of viruses. publish, saying that they are only pointing never stop vaccinating against polio. “You US government officials have been floating out the fact that terrorists could misuse cannot eliminate a virus from existence,” he the idea of such restrictions since the terror- published data. “We’ve been criticized for says. “Somebody can always resynthesize it, ist attacks last autumn (see Nature 414, playing into the hands of a bioterrorist, but and that’s a scary realization.” 237–238; 2001).
    [Show full text]
  • Defective Interfering Particles of Poliovirus I
    JOURNAL OF VIROLOGY, Apr. 1971, p. 478-485 Vol. 7, No. 4 Copyright © 1971 American Society for Microbiology Printed int U.S.A. Defective Interfering Particles of Poliovirus I. Isolation and Physical Properties CHARLES N. COLE, DONNA SMOLER, ECKARD WIMMER, AND DAVID BALTIMORE Departmenit of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Received for publication 8 January 1971 A class of defective interfering (DI) poliovirus particles has been identified. The first was found as a contaminant of a viral stock; others have been isolated by serial passage at a high multiplicity of infection. The DI particles are less dense than standard virus and sediment more slowly. Their ribonucleic acid (RNA) sediments more slowly than standard RNA and has a higher electrophoretic mobility. Compe- tition hybridization experiments with double-stranded viral RNA indicate that DI RNA is 80 to 90'- of the length of standard RNA. The proteins of DI particles are indistinguishable from those of standard poliovirus. Defective interfering (DI) particles are found (ii) virus diluted serially in medium; (iii) HeLa cells in stocks of many different types of viruses (9). washed twice with medium and resuspended at 107/ml These particles are a natural form of mutant in medium plus 1 horse serum. A mixture of 0.2 which could be useful in the study of viral multi- ml of a given virus dilution with 0.6 ml of cells and 0.6 ml of agar were spread rapidly over base layer plication. They are also of interest because of plates at room temperature, and plates were incu- their possible role in viral disease processes (9).
    [Show full text]
  • Synthetic Biology: Synthesis and Modification of a Chemical Called Poliovirus
    Synthetic biology: Synthesis and modification of a chemical called poliovirus Steffen Mueller, Dimitris Papamichail, John Robert Coleman, Jeronimo Cello, Aniko Paul, Steven Skiena, and Eckard Wimmer SUNY–Stony Brook, U.S.A. Synthetic biology is a newly emerging scientific field, encompassing knowledge of different disciplines, such as engineering, physics, chemistry, computer sciences, mathematics, and biology. Synthetic biology aims to create novel biological systems with functions that do not exist in nature. There seem infinite possibilities of constructing unique derivatives of existing organisms (bacteria, yeast, viruses). Apart from designing novel building elements for engineering biological systems, a fundamental requirement in synthetic biology is the ability of large-scale DNA synthesis and DNA sequencing. Viruses can be described in chemical terms; the empirical formula of the organic matter of poliovirus being:1 C332,652H492,388N98,245O131,196P7,501S2,340. Placing these atoms into order, a particle of high symmetry emerges2 with all the properties required for its proliferation and “survival” in nature. These properties are encoded in the viral genome, which is a single stranded nucleic acid (RNA) of about 7,500 nucleotides. Guided by the published nucleotide sequence,3 we have recently synthesized the DNA equivalent of the polio RNA genome and converted it by simple biochemical manipulations in a cell-free environment (outside living cells) into authentic poliovirus particles.4 The synthesis of a replicating "organism" in the absence of a natural template was without precedence at the time of publication4 and it provoked widespread responses – good and bad. Poliovirus is a human virus that replicates after ingestion in the gastrointestinal tract.
    [Show full text]
  • Doctor Atomic and Doctor Genomic
    GENDER MEDICINE/VOL. 5, NO. 4, 2008 Editorial Doctor Atomic and Doctor Genomic As I watched Doctor Atomic, John Adams’ fascinating new production with The Metropolitan Opera that dramatizes the Manhattan Project’s creation of the atomic bomb, I applauded the brilliant portrayal of the dilemma that our greatest scientific achievements pose. Because of their completely novel and tremen- dous power, these achievements have the potential for both enormous good and unimaginably terrible consequences. The opera’s libretto used original sources, and in their own words described the gut-wrenching tensions among the scientists involved in making the bomb. No imagined dialogue could possibly have been more compelling. Edward Teller and Robert Wilson tried, unsuccessfully, to persuade their colleagues to petition President Truman to refrain from dropping the bomb on Japan. Yet Robert Oppenheimer, the complex, highly cultured, and charismatic project leader whom Adams dubbed “Dr. Atomic,” pushed the testing of the device to completion, despite his own misgivings. He later said, “As I watched the explosion, I thought of a quotation from the Bhagavad Gita: ‘I am become death, the destroyer of worlds.’” The average age of the more than 300 men and women who worked on the Manhattan Project was 25. At Los Alamos, beer drinking, lovemaking, and frenzied devotion to finishing the project were all, predict- ably, going on at once. Many worked to the point of exhaustion: one young scientist was hospitalized with a nervous breakdown. The opera touched on the thousand difficulties faced by Oppenheimer as he knit the project together despite the disparate enthusiasms, misgivings, and diametrically opposed moti- vations of the gifted scholars, many of them Nobel laureates, who worked to complete it.
    [Show full text]
  • Discover the World of Microbes Related Titles
    Gerhard Gottschalk Discover the World of Microbes Related Titles Dale, J. W., Park, S. F. Molecular Genetics of Bacteria 2010 ISBN: 978-0-470-74184-9 Krämer, R., Jung, K. (eds.) Bacterial Signaling 2010 ISBN: 978-3-527-32365-4 Feldmann, H. Yeast Molecular and Cell Biology 2010 ISBN: 978-3-527-32609-9 Wiegel, J., Maier, R., Adams, M. (eds.) Incredible Anaerobes From Physiology to Genomics to Fuels ISBN: 978-1-57331-705-4 Wilson, M. Bacteriology of Humans An Ecological Perspective 2008 ISBN: 978-1-4051-6165-7 Gerhard Gottschalk Discover the World of Microbes Bacteria, Archaea, and Viruses The Author Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in Prof. Dr. Gerhard Gottschalk preparing this book, they make no representations Institut für Mikrobiologie und or warranties with respect to the accuracy or Genetik completeness of the contents of this book and Georg-August-Universität specifically disclaim any implied warranties of Grisebachstr. 8 merchantability or fitness for a particular purpose. 37077 Göttingen No warranty can be created or extended by sales Germany representatives or written sales materials. The advice and strategies contained herein may not be Cover suitable for your situation. You should consult with The cover was designed by Anne a professional where appropriate. Neither the Kemmling, Göttingen. Source of publisher nor authors shall be liable for any loss of the micrographs (left to right: profit or any other commercial damages, including row 1, Anne Kemmling; row 2, but not limited to special, incidental, consequential, Manfred Rohde, Braunschweig, or other damages.
    [Show full text]
  • Celebratory Speech by Professor Dr
    Laudatio by Prof. Dr. Hans-Georg Kräusslich for Prof. Dr. Eckard Wimmer [Check against delivery.] [Address] “A Heart for Viruses” - that was the title of an article on Eckard Wimmer in the ‘My Career – Jobs and Opportunities’ column in the German newspaper Frankfurter Allgemeine Zeitung this July. It is surely no coincidence that Ernst-Ludwig Winnacker, the 2011 Robert Koch Gold Medal winner wanted to call one of his books “I Love Viruses”. Given that these pathogens cause many diseases, this title was deemed to have too much potential for misunderstanding, and changed to “Viruses, the Secret Rulers” in the end. This fascination with the astonishing properties of these miniscule pathogens and their importance for the evolution and development of illnesses is what unites Eckard Wimmer and Ernst-Ludwig Winnacker, and forms a link to last year’s award. By awarding him the Robert Koch Gold Medal, we are now honouring Eckard Wimmer's life's work and his great contribution to polio virus research, and to the development of molecular virology as a whole. Eckard Wimmer is a chemist, as evidenced by the way he approaches his research subjects and what drives him in his work. Of course, this is mainly the desire to understand an important pathogen and its ability to reproduce and spread, as well as to explain its pathogenic potential. He concentrated on the virus which causes infantile paralysis, the polio virus, an ancient pathogenic virus that wreaked havoc on mankind for many centuries. Today, the polio virus is one of the most thoroughly studied viruses, in no small part thanks to Eckard Wimmer’s research.
    [Show full text]
  • Effects of TDP2/Vpg Unlinkase Activity on Picornavirus Infections
    viruses Article Effects of TDP2/VPg Unlinkase Activity on Picornavirus Infections Downstream of Virus Translation 1, 2, 2 1, Autumn C. Holmes y, Guido Zagnoli-Vieira z , Keith W. Caldecott and Bert L. Semler * 1 Department of Microbiology & Molecular Genetics and Center for Virus Research, University of California, Irvine, CA 92697, USA; [email protected] 2 Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, UK; [email protected] (G.Z.-V.); [email protected] (K.W.C.) * Correspondence: [email protected] Present address: Department of Infectious Disease, Washington University School of Medicine, y St. Louis, MO 63110, USA. Present address: The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, z Cambridge CB2 1QN, UK. Received: 28 December 2019; Accepted: 22 January 2020; Published: 31 January 2020 Abstract: In this study, we characterized the role of host cell protein tyrosyl-DNA phosphodiesterase 2 (TDP2) activity, also known as VPg unlinkase, in picornavirus infections in a human cell model of infection. TDP2/VPg unlinkase is used by picornaviruses to remove the small polypeptide, VPg (Virus Protein genome-linked, the primer for viral RNA synthesis), from virus genomic RNA. We utilized a CRISPR/Cas-9-generated TDP2 knock out (KO) human retinal pigment epithelial-1 (hRPE-1) cell line, in addition to the wild type (WT) counterpart for our studies. We determined that in the absence of TDP2, virus growth kinetics for two enteroviruses (poliovirus and coxsackievirus B3) were delayed by about 2 h. Virus titers were reduced by ~2 log10 units for poliovirus and 0.5 log10 units for coxsackievirus at 4 hours post-infection (hpi), and by ~1 log10 unit at 6 hpi for poliovirus.
    [Show full text]