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1 2 Small Pox Ebola – filamentous form – 60-80nm in diameter, on average 1000 nm long (but highly variable) Chickenpox virus Polio Virus Influenza virus HIV virus Hepatitis – this one actually Hepatits B magnified 120,000X Foot and Mouth disease – 1967 outbreak in the UK saw the destruction of 400,000 animals Viruses are most numerous “microorganisms” on the planet. Infect ALL types of cellular organisms All viruses are the same (strategically)! Viruses package their genome into a particle which is then infectious The viral genome has all of the information that it needs to attach and enter the host, decode its genome, allow for its proteins to be made, replicate its genome and then assemble and release virus particles. Viruses establish themselves in a host community to survive 3 Viruses Extracellular state virus particle or virion Intracellular state viral replication infection Extracellular minute particle containing nucleic acid surrounded by protein and sometimes other macromolecular components METABOLICALLY INERT – does not carry out respiratory or biosynthetic functions The virion is a way for the virus genome to get from cell to cell Intracellular infections HOST – cell in which a virus can infect and once inside the virus can replicate 4 Viruses Characteristics Small Obligate intracellular parasite Crystallizable Nucleic Acid DNA or RNA Protein coat Capsid Envelope – Not all viruses lipid, protein, carbohydrate NOT susceptible to antibacterial drugs The discovery of viruses Ivanowsky, 1892, the agent which causes tobacco mosaic disease is not retained by filters Beijerinck, 1898, same observation, proposed small agent 1898, foot and mouth disease similar Could not be isolated in pure culture! Required hosts for replication Contagium vividum fluvium -> (ultra)filterable virus -> virus Bacteriophage, 1915 Twort and d'Herelle, 1917 Small -- Range from 20 to 300nm in diameter. 200nm is just smaller than the smallest bacterium, while smallpox virus at 28nm is about the size of a ribosome! Obligate intracellular parasite Crystallizable Nucleic Acid DNA or RNA Protein coat Capsid Envelope – Not all viruses lipid, protein, carbohydrate NOT susceptible to antibacterial drugs 5 TABLE 9.1 Some types of viral genomes Viral Genome Virus Host Type of nucleic acid in virion structure Number of molecules Size H-l parvovirus Animals ssDNA Linear 1 5.1kb φX174 Bacteria ssDNA Circular 1 5.4kb Simian virus 40 (SV40) Animals dsDNA Circular 1 5.2kb Poliovirus Animals ssRNA Linear 1 7.4kb Cauliflower mosaic virus Plants dsDNA Circular 1 8.0kb Cowpea mosaic virus Plants ssRNA Linear 2 different 9.4kb total Reovirus type 3 Animals dsRNA Linear 10 different 23.5kb total Bacteriophage lambda Bacteria dsDNA Linear 1 48.5kb Herpes simplex virus type I Animals dsDNA Linear 1 152.3kb Bacteriophagc T4 Bacteria dsDNA Linear 1 168.9kb Human cytomegalovirus Animals dsDNA Linear 1 229.4kb Despite the diversity of viral genomes they all follow the CENTRAL DOGMA of molecular biology nucleic acid => protein 6 Viruses Capsid – Nucleic acid enclosed inside Structural subunits arranged in highly precise and repetitive pattern Few viruses single protein as capsid Most viruses have several are chemically distinct are associated with each other in specific ways to form Capsomers.. Capsomer – the morphological unit that can be seen with the electron microscope. Nucleocapsid == complete complex of nucleic acid and protein, packaged in the virion. 7 Viruses Viral Symmetry Helical Symmetry Icosahedral Symmetry Helical == rod shapped TMV Icosahedral = Spherical rougly spherical 20 faces simplest is 3 morphological units per face for a total of 60 units per virus particle 3 units could be identical or different HERPES VIRUS The HSV-1 capsid is an icosahedral shell 15 nm thick and 125 nm in diameter. It is composed of 162 capsomers (12 pentons and 150 hexons) which can be seen in the capsid reconstruction shown at the left. Representative pentons are shown in orange and hexons in red.The capsomers lie on a T=16 icosahedral lattice. They are connected in groups of three by trivalent structures called triplexes (green) that lie above the capsid floor and connect the capsomers in groups of three. There are a total of 320 triplexes in the capsid. The capsid mass is approximately 200 MDa without the DNA and 300 MDa with DNA. 8 Viruses Enveloped Viruses Complex membranous structure surrounds the nucleocapsid lipid bilayer from host proteins viral Why might a viral envelope consisting of the hosts cell membrane be advantageous? What part of an enveloped virus would first contact the cell? Host immune system 9 Viruses Virus Host Range Main determinant of host recognition cell surface receptors Restriction modification enzymes Restriction endonuclease Viral DNA glucosylate or methylate Cell surface receptors specific proteins, or glycoprotein or polysaccharides e. Coli bacteriophage would not attach to s. aureus no recognizable receptor on s. aureus CAT virus would not infect Human Monkey virus might with modification/mutation? Simian Virus 40 SV40 and Mesothelioma NOT a factor SV40 was a contaminant in polio vaccines T-even bacteriophage 5’hydroxymethylcytosine == modified cytosine not recognized by RE in this form 10 Viruses Viral multiplication Best understood in Bacteriophages – T even phage of E. coli dsDNA - linear 100 genes Complex Architecture both icosahedrol and helical 11 Viruses Adsorption Penetration Biosynthesis of viral components Maturation Release Adsorption – tail fibers to receptor on E. coli cell surface -- CHANCE COLLISION Penetration – inject DNA, empty phage (ghost) stays on the outside. Contraction, lysozyme degrades peptidoglycan energy ATP from tail fibers Biosynthesis of Viral Components Viral DNA hijacks host cells metabolic machinery Host DNA is degradded == stops transcriptiion of host DNA DNA replicated mRNA Proteins synthesized DNA=> mRNA=> protein very much time dependent Early-early enzymes Mid Nucleic acid replication and transcription late synthesis and assembly of virions and viral proteins. Maturation components assembled to mature viruses USE WILKINSON”S DIAGRAM -- SEE NOTES Release lysozyme produced, degrades peptidoglycan, cell lyses (bursts) phage are liberated. Approx 100 phage per cell 12