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Lec 1 Virology 2016-2017 *Introduction Viruses are the smallest infectious agents (ranging from about 20 nm to about 300 nm in diameter) and contain only one kind of nucleic acid (RNA or DNA) as their genome. The nucleic acid is encased in a protein shell(capsid), which may be surrounded by a lipid-containing membrane. The entire infectious unit is termed a virion. Viruses are inert in the extracellular environment; they replicate only in living cells, being parasites at the genetic level. The viral nucleic acid contains information necessary for programming the infected host cell to synthesize virusspecific macromolecules required for the production of viral progeny. The virus infection may have little or no effect on the host cell or may result in cell damage or death. Viruses are known to infect unicellular organisms such as mycoplasmas, bacteria, and algae and all higher plants and animals. Figure (1) Schematic diagrams of viruses 1 *Evolutionary Origin of Viruses The origin of viruses is not known. There are profound differences among the DNA viruses, the RNA viruses, and viruses that utilize both DNA and RNA as their genetic material during different stages of their life cycle. It is possible that different types of agents are of different origins. Two theories of viral origin can be summarized as follows: 1-Viruses may be derived from DNA or RNA nucleic acid components of host cells that became able to replicate autonomously and evolve independently. They resemble genes that have acquired the capacity to exist independently of the cell. 2-Viruses may be degenerate forms of intracellular parasites. There is no evidence that viruses evolved from bacteria, though other obligately intracellular organisms, eg, rickettsiae and chlamydiae, presumably did so. However, poxviruses are so large and complex that they might represent evolutionary products of some cellular ancestor. *Classification of Viruses Basis of Classification The following properties have been used as a basis for the classification of viruses. 1-Virion morphology, including size, shape, type of symmetry, presence or absence of peplomers, and presence or absence of membranes 2-Virus genome properties, including type of nucleic acid (DNA or RNA), size of genome in kilobases (kb) or kilobase pairs (kbp), strandedness (single or double), whether linear or circular, sense (positive, negative, ambisense), segments (number, size), nucleotide sequence, G + C content, and presence of special features (repetitive 2 elements, isomerization, 5'-terminal cap, 5'-terminal covalently linked .)protein, 3'-terminal poly(A) tract 3-Physicochemical properties of the virion, including molecular mass, buoyant density, pH stability, thermal stability, and susceptibility to physical and chemical agents, especially ether and detergents 4-Virus protein properties, including number, size, and functional activities of structural and nonstructural proteins, amino acid sequence, modifications (glycosylation, phosphorylation, myristylation), and special functional activities (transcriptase, reverse transcriptase, neuraminidase, .)fusion activities 5-Genome organization and replication, including gene order, number and position of open reading frames, strategy of replication (patterns of transcription, translation), and cellular sites (accumulation of proteins, .)virion assembly, virion release 6-Antigenic properties 7-Biologic properties, including natural host range, mode of transmission, .vector relationships, pathogenicity, tissue tropisms, and pathology *Universal System of Virus Taxonomy A system has been established in which viruses are separated into major groupings called families on the basis of virion morphology, genome structure, and strategies of replication. Virus family names have the suffix -viridae *Definition of some terminology : 1-Viroids Small infectious agents that cause diseases of plants. Viroids are agents that do not fit the definition of classic viruses. They are nucleic acid molecules (MW 70,000–120,000) without a protein coat. e,g :Plant viroids are single-stranded, covalently closed circular RNA molecules, 3 viroids have been detected only in plants; none have been demonstrated to exist in animals or humans. 2-Prions Infectious particles composed solely of protein with no detectable nucleic acid. Highly resistant to inactivation by heat, formaldehyde, and ultraviolet light that inactivate viruses. The prion protein is encoded by a single cellular gene. Prion diseases, called "transmissible spongiform encephalopathies," include scrapie in sheep. 3- Virusoids : groups of satellite RNA discovered in covers of certain viruses replication by assistant virus . *Measuring the Sizes of Viruses Small size and ability to pass through filters that hold back bacteria are classic attributes of viruses. However, because some bacteria may be smaller than the largest viruses, filterability is not regarded as a unique feature of viruses Direct observation in the electron microscope is the most widely used method for estimating particle size. Viruses can be visualized in preparations from tissue extracts and in ultrathin sections of infected cells. Another method that can be used is sedimentation in the ultracentrifuge. In an ultracentrifuge, forces of more than 100,000 times gravity may be used to drive the particles to the bottom of the tube. The relationship between the size and shape of a particle and its rate of sedimentation permits determination of particle size. Chemical Composition of Viruses 1-Viral Proteins ( including capsid ) The structural proteins of viruses have several important functions. First Their major purpose is to facilitate transfer of the viral nucleic acid from one host cell to another. Second They serve to protect the viral genome against inactivation by nucleases, third participate in the attachment of the virus particle to a susceptible cell, and provide the structural 4 symmetry of the virus particle. Some viruses carry enzymes (which are .proteins) inside the virions. Note :The proteins determine the antigenic characteristics of the virus. 2-Viral Nucleic Acid Viruses contain a single kind of nucleic acid either DNA or RNA that encodes the genetic information necessary for replication of the virus. The genome may be single-stranded or double-stranded, circular or linear, and segmented or nonsegmented. The type of nucleic acid, its strandedness, and its size are major characteristics used for classifying viruses into families. 3-Viral Lipid Envelopes A number of different viruses contain lipid envelopes as part of their structure. The lipid is acquired when the viral nucleocapsid buds through a cellular membrane in the course of maturation. 4-Viral GlycoproteinsViral envelopes contain glycoproteins. In contrast to the lipids in viral membranes, which are derived from the host cell, the envelope glycoproteins are virus-encoded. However, the sugars added to viral glycoproteins often reflect the host cell in which the virus is grown It is the surface glycoproteins of an enveloped virus that attach the virus particle to a target cell by interacting with a cellular recepter. 5 Figure (2) Budding by influenza virus *Cultivation & Assay of Viruses Many viruses can be grown in cell cultures or in fertile eggs under strictly controlled conditions. Growth of virus in animals is still used for the primary isolation of certain viruses and for studies of the pathogenesis of viral diseases and of viral oncogenesis. Diagnostic laboratories attempt to recover viruses from clinical samples to establish disease. Research laboratories cultivate viruses as the basis for detailed analyses of viral expression and replication. Cells grown in vitro are central to the cultivation and characterization of viruses. There are three basic types of cell cultures 1-Primary cultures are made by dispersing cells (usually with trypsin) from freshly removed host tissues. In general, they are unable to grow for more than a few passages in culture. 6 2-Diploid cell lines are secondary cultures which have undergone a change that allows their limited culture (up to 50 passages) but which retain their normal chromosome pattern. 3-Continuous cell lines are cultures capable of more prolonged perhaps indefinite—growth that have been derived from diploid cell lines or from malignant tissues. They invariably have altered and irregular numbers of chromosomes. The type of cell culture used for viral cultivation depends on the sensitivity of the cells to a particular virus. Note : Questions expected about this lecture : 1- mention the functions for viruses protein . 2- How diagnose the viruses in vitro and in vivo? 3- Define the following terms : virion , viroid , virusoid and prion ̋ *With best greeting* 7