Lecture # 1: Course Introduction

Transcription

1 Lecture # 1: Course Introduction I. Instructor and Background Dr. Richard Kuhn rjkuhn@bragg.bio.purdue.edu B-129 Lilly Hall Office Hours - Wednesday 10:30-11:30 II. Objective: To use viruses as a vehicle to: 1) Study disease 2) Examine how viruses provide ideal model systems for unraveling how the cell itself functions. 3) Demonstrate the potential of using viruses to deliver genes and other novel therapeutic approaches III. What are the requirements for taking and passing this course? 1) Core biology courses 2) The ability to blend fundamental principles from biology, chemistry, and physics 3) A little curiosity and some work Spring

2 IV. Course syllabus: 1. Course limited to eukaryotic host-viral systems 2. Two different phases to the course: a) Introduction to viral processes b) An examination of specific viral systems V. Description of class mechanics 1. Lecture format: a. Lecture with research examples b. Straight memorization will not help you: apply principles! c. Ask questions or I will ask questions of you 2. Texts Viruses and Human Disease (Strauss & Strauss) 2002 Fundamentals of Molecular Virology (Acheson) 2002 Reference: Principles of Virology (Flint, Enquist, Krug, Racaniello, Skalka) Not required but good reading and diagrams 3. Lecture notes: will be available as PDFs on the web. 4. Exams: 3 exams equal weight (33% each exam). a. Final is not cumulative (covers only last 1/3) b. Format of exams: short answer/ T/F/ thinking essays c. Approach to passing exams: apply principles Spring

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5 1798 Jenner 5 the pox INTRODUCTION

6 Jenner Iwanowski, Beijerinck, Loeffler & Frosch Infective Bacteria-Free Filtrate 6 INTRODUCTION

7 Early Discovery of Infectious Agents Spring

8 Early Landmarks in Virus Research Date Virologist Discovery late 1800 s Koch Filterable agents, Koch s postulates 1898 Loeffler & Frosch First demonstration of a filterable animal virus, foot and mouth virus 1901 Reed Identification of Yellow fever virus 1909 Landsteiner & Popper Transmission of CNS fluid from child to monkey establishes a virus as a causative agent for poliomyelitis 1911 Rous Identified virus causing solid tumors, Rous sarcoma virus 1931 Woodruff Use of embryonic hen s egg as a viral host 1933 Smith Isolation of Influenza 1949 Enders Nonneuronal tissue supports poliovirus replication in culture 1952 Dulbecco Development of virus plaque assay 1952 Hershey & Chase Nucleic acid is the genetic material 1950s Salk & Sabin Development of killed and attenuated poliovirus vaccines 1972 Temin & Baltimore Discovery of reverse transcriptase 1984 Montagnier & Gallo Isolation of HIV as the causative agent for AIDS Spring

9 Nobel Prizes involving Virology* Year Names Nobel Citation; Virus Group or Family 1946 [Chemistry] Wendell Stanley Isoation, purification and crystallization of tobacco mosaic virus; Tobamovirus 1951 Max Theiler Development of yellow fever vaccine; Flaviviridae 1954 John F. Enders, Thomas Weller, Frederick C. Robbins Growth and cultivation of poliovirus; Picornaviridae 1958 Joshua Lederberg Transforming bacteriophages 1965 Francois Jacob, André Lwoff Jacques Monod Operons; bacteriophages 1966 Francis Peyton Rous Discovery of tumor-producing viruses; Retroviridae 1969 Max Delbruck, Alfred D. Hershey, Salvador E. Luria Mechanism of virus infection in living cells; bacteriophages 1975 David Baltimore, Howard M. Temin, Renato Dulbecco Discoveries concerning the interaction between tumour viruses and the genetic material of the cell; Retroviridae 1976 D. Carleton Gajdusek Baruch S. Blumberg New mechanisms for the origin and dissemination of infectious diseases; B with Hepadnaviridae, G with prions ** Daniel Nathans Application of restriction endonucleases to the study of the genetics of SV40; Polyomaviridae 1980 [Chemistry] Paul Berg Studies of the biochemistry of nucleic acids, with particular regard to recombinant DNA (SV40);Polyomaviridae 1982 [Chemsitry] Aaron Klug Development of crystallographic electron microscopy and structural elucidation of biologically important nucleic acidprotein complexes;tobamovirus and Tymovirus ** 1988 George Hitchings Gertrude Elion Important principles of drug treatment using nucleotide analogs (acyclovir) 1989 J. Michael Bishop, Harold E. Varmus Discovery of the cellular origin of retroviral oncogenes; Retroviridae 1993 Phillip A. Sharp Richard J. Roberts Discoveries of split (spliced) genes; Adenoviridae 1996 Rolf Zinkernagel Peter Doherty 1997 Stanley Prusiner Prions Presentation of viral epitopes by MHC Spring * All prizes listed are in Physiology or Medicine except those three marked [Chemistry]. ** In these two instances, the prize was shared with unlisted recipients whose work did not involve viruses.

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11 Properties of Viruses A. Definitions: 1. Obligate intracellular parasites with a relatively simple life cycle and/or 2. Viruses are entities whose genomes (nucleic acids) replicate inside living cells using the cellular biosynthetic machinery and cause the synthesis of specialized elements (virions) that can transfer the viral genome to other cells. B. Small in size can pass through bacteriological filters C. Viruses contain no enzymes used for energy production. Some do contain enzymes associated with nucleic acid metabolism. D. contain only one type of nucleic acid. 1. RNA, double stranded or single stranded. 2. DNA, double stranded or single stranded. 3. Nucleic acid is main component of virion (plus coat) 4. Some viruses have enzymes in virion particles. Viruses E. Replicate through an assembly-line like mechanism in the host cell use host cell metabolic machinery to synthesize all of the necessary viral components and then assemble them into virus particle - simple nature of life cycle compared to that of a eukaryotic cell. Spring

12 Properties of Viruses (cont d) F. Viruses known to infect nearly all organisms. 1. Bacteria - bacteriophages. 2. Plants - RNA or DNA containing viruses as well as agents called viroids. 3. Insects - numerous viruses infect insects; certain viruses are transmitted to both plants and animals via insect vectors. 4. Higher animals Spring

13 Levels of Analysis: Molecular:» Cell Biology» Biochemistry» Genetics» Structure Clinical (organism): Pathogenesis - disease patterns - organs and tissues affected - immune response Population Groups: Epidemiological Spring

14 The study of viruses require: 1) Isolate virus and quantitate 2) Propagate and manipulate a. animal model replication and pathogenesis b. cell culture replication and genetics 3) In vitro biochemistry a. develop enzymatic assays b. study virus assembly c. determine three-dimensional structure of virus particle and viral proteins Spring

15 Scale of Viruses Spring

16 VI + RNA DNA IV + RNA - RNA + or - DNA II + - DNA I + mrna III + - RNA V - RNA 16 CLASSIFICATION

17 RETROVIRIDAE PICORNAVIRIDAE TOGAVIRIDAE FLAVIVIRIDAE CALICIVIRIDAE CORONAVIRIDAE VI + RNA DNA IV + RNA - RNA + or - DNA + mrna - RNA PARVOVIRIDAE HEPADNAVIRIDAE PAPOVAVIRIDAE ADENOVIRIDAE HERPESVIRIDAE POXVIRIDAE REOVIRIDAE BUNYAVIRIDAE ARENAVIRIDAE RHABDOVIRIDAE PARAMYXOVIRIDAE ORTHOMYXOVIRIDAE 17 CLASSIFICATION II + - DNA I V III + - RNA

18 Classification Scheme for Animal RNA Viruses Spring

19 Classification Scheme for Animal DNA Viruses Spring

20 Web Sites of Interest to Virologists 1. (Has links to almost all the virology sites on the web) (A list of ICTV-approved virus names and links to virus databases) 6. Spring