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Medical Virology Introduction Dr. Sameer Naji, MB, BCh, PhD (UK) Dean Assistant Head of Basic Medical Sciences Dept. Faculty of Medicine The Hashemite University General Properties of Viruses Viruses are the smallest infectious agents. Most forms of life – animals, plants and bacteria – are susceptible to infection with appropriate viruses. Properties that distinguish viruses from other microorganisms.: 1. They are obligate intracellular parasites 2. They are inert (nucleoprotein ) filterable Agents 3. Small size: viruses are smaller than other organisms, vary in size (diameter) from 10 nm - 300 nm. 4. Genome: either DNA or RNA. The nucleic acid is encased in a protein shell, which may be surrounded by a lipid – containing membrane. The entire infectious unit is termed a virion. 5. Metabolically inert: Viruses have no metabolic activity outside susceptible host cells; they do not possess any ribosomes or protein-synthesizing apparatus, cannot make energy or proteins independent of a host cell, therefore, they multiply only in living cells. On entry, the genome or nucleic acid is transcribed into – or acts as – mRNA which then directs the replication of new virus particles. Virus vs. Cells Property Type of nucleic acid Proteins Lipoprotein membrane Ribosomes Mitochondria Viruses DNA or RNA Few Enveloped present in some viruses Absent Absent Enzymes Multiplication by binary fission None or few No Cells DNA and RNA Many Cell membrane present in all cells Present Present in eukaryotic cells Many Yes (most cells) Viruses are Ultramicroscopic The size of viruses Terms & Definitions in Virology: Capsid: the protein shell, or coat, that encloses the nucleic acid genome. Capsomeres: morphologic units seen in the electron microscope on the surface of icosahedral virus particles. They represent clusters of polypeptides. Defective virus: a virus particle that is functionally deficient in some aspect of replication. - Envelope: a lipid-containing membrane that surrounds some virus particles. It is acquired during viral maturation by a budding process through a cellular membrane. - Nucleocapsid: the protein-nucleic acid complex representing the packaged form of the viral genome (capsid + genome). - Structural units: the basic protein building blocks of coat. - Subunit: a single folded viral polypeptide chain. - Virion: the complete intact virus particle. Sometimes it is identical with the nucleocapsid (as in papillomaviruses). In more complex virions (as herpesviruses), this includes the nucleocapsid plus a surrounding envelope. Viral Structure - Overview Nucleic acid Nucleocapsid Capsid Envelope protein Membrane protein Spike protein Viral envelope** Schematic overview of the structure of animal viruses ** does not exist in all viruses Naming viruses • No taxa above Family (no kingdom, phylum, etc) • Classified based on structures, size, nucleic acids, host • • • • • species, target cells. 20 families of animal viruses (7 DNA, 13 RNA) Family name ends in – viridae Subfamily ends in — virinae Genus name ends in – virus Species – – – – – Example Family – Herpesviridae Subfamily - Herpesvirinae Genus – Simplex virus Common name – herpes virus (Herpes simplex virus I (HSV-I) Disease – fever blisters, cold sores How are viruses named? Based on: - the disease they cause poliovirus, rabies virus - the type of disease murine leukemia virus - geographic locations Sendai virus, Coxsackie virus - their discovers Epstein-Barr virus - how they were originally thought to be contracted dengue virus (“evil spirit”), influenza virus (the “influence” of bad air) - combinations of the above Rous Sarcoma virus Structure of Viruses Viruses consist basically of a core of nucleic acid surrounded by a protein coat which is antigenic and specific for each virus type; it protects viral genome from inactivation by adverse environmental as nucleases in blood stream. Structures which make up a virus particle are: Virion, Capsid, Capsomeres, Nucleic acid, and Envelope. It varies in size, shape and symmetry Virus particles show three types of capsid symmetry: 1. Cubic: in which the particles are icosahedral protein shells with nucleic acid contained inside, has 20 faces, each an equilateral triangle. e.g. adenovirus. 2. Helical: Protein binds around DNA/RNA in a helical fashion (in which the particle is elongated and in the form of a helix or spiral). Most viruses posses an outer envelope. e.g. Coronavirus 3. Complex: in which the particle does not confirm either, e.g. poxvirus . 5 BASIC TYPES OF VIRAL STRUCTURE icosahedral nucleocapsid nucleocapsid lipid bilayer ICOSAHEDRAL ENVELOPED ICOSAHEDRAL helical nucleocapsid COMPLEX nucleocapsid lipid bilayer glycoprotein spikes = peplomers HELICAL ENVELOPED HELICAL VIRAL STRUCTURE (virion) 1. Protect genome during passage from one cell to another 2. Aid in entry process 3. Package enzymes for early steps of infection CAPSID STRUCTURE 1. Helical capsid Rod-shaped capsomers Coil around hollow center Nucleic acid is kept inside – wound-up within tube (Helix ) Morphological types Morphological types Helical – capsid surrounds RNA like hollow tube Ex: Influenza , measles, rabies (enveloped) Helical symmetry Morphological types 2. icosahedral PROTOM ER 20-sided with 12 corners Vary in the number of capsomers Each capsomer may be made of 1 or several proteins Some are enveloped Cubic or icosahedral symmetry ICOSAHEDRAL SYMMETRY Adenovirus Enveloped helical virus Enveloped icosahedral virus Helical California Encephalitis Virus Coronavirus Hantavirus Influenza Virus (Flu Virus) Measles Virus ( Rubeola) Mumps Virus Para influenza Virus Rabies Virus Respiratory Syncytial Virus(RSV) Icosahedral Adeno-associated Virus (AAV) Adenovirus B19 Coxsackievirus - A Coxsackievirus - B Cytomegalovirus (CMV) Eastern Equine Encephalitis Virus (EEEV) Echovirus Epstein-Barr Virus (EBV) Hepatitis A Virus (HAV) Hepatitis B Virus (HBV) Hepatitis C Virus (HCV) Hepatitis Delta Virus (HDV) Hepatitis E Virus (HEV) Herpes Simplex Virus 1 (HHV1) Herpes Simplex Virus 2 (HHV2) Human Immunodeficiency Virus (HIV) Human T-lymphotrophic Virus (HTLV) Norwalk Virus Papilloma Virus (HPV) Polio virus Rhinovirus Rubella Virus Saint Louis Encephalitis Virus Varicella-Zoster Virus (HHV3) Western Equine Encephalitis Virus (WEEV) Yellow Fever Virus Complex viruses Have additional or special structures Examples: Poxviruses – lack normal capsid – instead, layers of lipoprotiens and fibrils on surface surface view cross section A bacteriophage A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid. The genetic material can be ssRNA, dsRNA, ssDNA, or dsDNA ('ss' or 'ds-' prefix denotes single-strand or double-strand) along with either circular or linear arrangement. Phage - viruses have a polyhedral head, helical tail and fibers for attachment.