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11/29/13 Relative Sizes of Viruses, Bacterial and Mammalian Cells Microbiology Lecture 5 Structure and Classification of Viruses Professor T.J. Foster Viruses • Infectious agents • DNA or RNA “genomes” • Nucleic acid protected by protein capsid • Depends on host cell for energy, building blocks (amino acids, nucleotides) and ribosomes. • Only propagates within host cell • Obligate intracellular parasites • Bacterial, plant, and animal viruses Definitions and Terminology • • • • Virion: complete virus particle Capsid: protein shell encasing genome Capsomer: protein subunit of capsid Nucleocapsid: capsid containing nucleic acid • Attachment protein: surface component for attachment to receptor on host cell – eg spike. Visible (by electron microscopy) attachment appendage (see adenovirus, next slide) 1 11/29/13 Diversity of Virus Capsid Shapes Spherical (Icosohedron) 20-faced polyhedron eg. Adenovirus 252 identical capsomers. Each capsomer has 6 neighbours (hexon). Except in 12 vertices, 5 neighbours (pentons) Diversity of Virus Capsid Shapes Tobacco Mosaic Virus • Rod (rigid filament) – Tobacco Mosaic Virus – Central hollow core – 49 capsomers every 3 turns – Helix – 1 capsomer protects 3 nucleotides X Ray crystal structure 2 11/29/13 Filamentous Viruses • Nucleocapsid - flexible helix • eg the paramyxovirus, the Mumps virus Complex • Cowpox virus (Vaccinia) – External surface series of parallel rows – Complex particle >100 proteins – Contains 2 membranes – Core nucleoprotein with at least 10 enzymes Bullet Shaped • eg the rabies virus Envelopes • Some animal viruses have a membranous outer envelope • Derived from host cell membrane • Contains viral glycoproteins (proteins with polysaccharide chains attached, synthesized in endoplasmic reticulum) – Host receptor recognition, attachment 3 11/29/13 Herpes Virus Structure The Five Basic Structural Forms • Naked Icosahedron – Adenovirus, poliovirus, • Naked helical (not found in animals) – Tobacco mosaic virus • Enveloped Icosohedron – Herpes virus, rubella virus, • Enveloped helical – Rabies virus, influenza virus, mumps virus, measles virus • Complex – Pox viruses Bacteriophage Viruses that Infect Bacteria Bacteriophage Icosohedral capsid contains nucleic acid Tail fibres. Attachment to bacterial cell surface Bacteriophage nucleocapsid does NOT enter bacterial cell. DNA is INJECTED through cell wall. Tail lysozyme degrades peptidoglycan. Sheath contracts. Syringe-like mechanism injects DNA into cytoplasm. 4 11/29/13 Classification. The Baltimore Scheme Based on Nucleic Acid Composition of Genome, Replication and Information Flow “Classification imposes order out of chaos” DNA REPLICATION ds DNA DNA polymerase DNA Double stranded ds DNA The Central Dogma Information Flow DNA > mRNA > Protein ds DNA 5 11/29/13 + _ TRANSCRIPTION TRANSCRIPTION + Baltimore Classification of Viruses Group Genome Transcription ds DNA Genetic Information. Example From genome to message dsDNA 1 ds DNA 2 ss DNA ssDNA 3 ds RNA dsRNA 4 + ss RNA dsRNA dsDNA mRNA Herpes simplex virus mRNA Parvovirus mRNA +ssRNA (mRNA) Reovirus Enterovirus Serves as mRNA 5 + ss mRNA + - ss RNA dsRNA -ssRNA mRNA Influenza dsDNA mRNA Retrovirus mRNA template 6 ssRNA ssRNA 7 Nicked ds DNA nicked ds intact ds mRNA Hepatitis B virus DNA DNA RNA replicate thru RNA intermediate 6 11/29/13 Adenovirus Baltimore 1. Double stranded DNA genome Non-enveloped icosohedron Common human pathogen Self-limiting upper respiratory tract infections Paramyxovirus Mumps and Measles Viruses Baltimore 5. Negative single-stranded RNA genomes Enveloped, filamentous [Vaccination: Measles Mumps Rubella (MMR)] Measles rash, raised spots. Middle ear infection. Pneumonia, Encephalitis (1:1000), Fatal (1:3000) Mumps Swollen parotid gland Influenza Virus Baltimore 5 Negative single strand RNA 8 segmented genome Enveloped, filamentous Seasonal ‘flu’ vaccine Herpes Virus Baltimore 1. Double stranded DNA. Enveloped icosohedron. Herpes infections of man. Herpes Simplex Viruses (HSV) Cold sore on lip Genital 7 11/29/13 Herpes Viruses Rubella Virus HSV-1 Baltimore 4. Positive stranded RNA genome Enveloped icosohedron Enters nerve cell German measles, mild rash Migrates to trigeminal ganglia near ear. Congenital rubella syndrome Foetal damage Virus remains dormant MMR Vaccine Re-activation Migrates to tip of nerve cell. Infects epithelial cells in lip. Retrovirus Baltimore 6 Positive single-stranded RNA plus reverse transcriptase Diploid Enveloped non-icosohedral elongated Human Immunodeficiency Virus (HIV) Acquired Immunodeficiency Diseases (AIDS) Pox Viruses Baltimore 1. Double stranded DNA Complex structure Smallpox 20% mortality. Scarring Vaccinia (cowpox) virus Jenner’s pioneering vaccination Eradicated by WHO vaccination programme No vaccine Anti-retrovirus drugs 8