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An Introduction to Viruses

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1 An Introduction to Viruses
Chapter 6 An Introduction to Viruses

2 General characteristics
Viruses = obligate, intracellular parasites that contain either DNA or RNA; depend on synthetic machinery of host cell for replication of the infectious particle called the virion Size - submicroscopic; most are beyond limit of resolution of light microscope (exception = poxviruses; can be seen under light microscope with proper illumination); size varies from 25 m to 250 m (approximately 0.1 diameter of E. coli cell)

3 Structural components
Nucleic acid core = genome - may be either DNA or RNA but never both; may be either single stranded (ss) or double stranded (ds); used in classification (ssDNA, ssRNA, dsDNA, or dsRNA); may be either linear or circular; found in all mature virus particles (virions)

4 Structural components
Protein coat = capsid - shell surrounding and protecting nucleic acid core; composed of identical subunits called capsomeres; subunits undergo self-assembly into geometric shapes around nucleic acid core; number of capsomeres is unique for each virus; contain receptors that combine with complementary sites on host cell surface for attachment; found in all mature viruses

5 Structural components
Envelope - lipid and protein membrane surrounding virion; origin = host cell membrane; lipid of envelope make viruses susceptible to lipid solvents and are more heat labile than non-enveloped viruses; found only in viruses that exit cell through cell membrane or bud through nuclear membrane during maturation; viruses without envelope are called naked Glycoprotein spikes - surface projections coded for by viruses; manufactured in host cell and become incorporated into host cell membrane prior to virion maturation; often act as receptors for host cells; may agglutinate rbc's

6 Shape Protein shell may assume either icosahedral (20 equilateral triangular faces = cubic symmetry) or helical (rod-shaped particles composed of repeating protein subunits surrounding core in a helical fashion = helical symmetry) shape; some viruses (e.g. poxviruses) have a complex shape

7 Classification of Viruses
Criteria for classification Nature of disease (e.g. neurotropic viruses) Organ system most frequently involved (e.g. hepatitis viruses) Physiochemical characteristics Type of nucleic acid (ssDNA, ssRNA, dsDNA, dsRNA) Presence or absence of envelope - ether sensitive are enveloped while ether resistant = naked Size (small = picornaviruses to large = poxviruses) Vertebrate viruses classified into 13 families of RNA-containing viruses and 7 families of DNA viruses

8 Replication Cycle

9 Attachment & Adsorption
cell surface phenomenon; adsorption involves specific interaction between sites on viruses and receptors on cell membrane of host cell via ionic or electrostatic interactions (e.g. HIV attaches via gp120 of virus to CD4 receptor on T cells); tropism = susceptibility of only certain cells to particular viral agent - may be related to presence or absence of receptors on host cell

10 Penetration usually occurs by phagocytosis (naked viruses) or fusion (enveloped viruses)

11 Uncoating & Biosynthesis
Uncoating - involves removal of protein coat and release of viral nucleic acid; may involve host enzymes (proteolytic) and/or viral coded enzymes brought in with virus or synthesized in new host Biosynthesis Involves synthesis of viral nucleic acid, viral coat proteins and virus-specific enzymes - each is synthesized separately Site of viral synthesis varies depending on type of NA; generalizations include: Most DNA viruses synthesize DNA in nucleus of host cell & proteins (structural & enzymatic) in cytoplasm Most RNA viruses synthesize all viral components in cytoplasm No infectious virus particles are detected during this period = eclipse period

12 Maturation (Assembly of virions)
Maturation (Assembly of virions) - involves combining of synthesized NA and protein; occurs in nucleus with most DNA viruses & cytoplasm with most RNA viruses; most capsids self-assemble around genome; defective (incomplete) viruses occur when NA is not coated by protein (empty coats or non-viral NA placed in coat)

13 Release Host cell disintegration (lysis) - occurs when cell fills with virus particles; causes death of cell and release of naked viruses Slow release through cell membrane as part of budding process - results in release of enveloped viruses; cell may not die for a long time & can continue to shed virus particles; some proteins synthesized under viral control become incorporated into CM of host and become incorporated into virion as virus buds through membrane (glycoprotein spikes); important in cellular immunity (proteins are antigenic and host recognizes these proteins as foreign mounting immune response against cells with these proteins in their membranes)

14 Effects of Viruses on Host Cells
Effects of viruses on host cells = cytopathic effects (CPE) – morphologic alterations that occur in virus-infected cells; often visible in light microscope Inclusions = intracellular structures; may be cytoplasmic or nuclear; represent aggregates of viral nucleic acid or protein, mature virions or degenerative cell reaction products; serve as markers of certain viral infections (e.g. Negri bodies = intracytoplasmic inclusions of rabies infection; Owl's eyes = cytomegaloviruses)

15 Effects of Viruses on Host Cells
Syncytia (multinucleated giant cells) - represent fusion of virus-infected cells with contiguous uninfected cells; form giant cells with many nuclei; caused by virus-induced changes in CM; allows cell to cell spread of virus without coming in contact with humoral immunity (e.g. respiratory syncytial viruses) Cell necrosis or death - rate of destruction depends on degree of shut-down of host cellular functions and rate of synthesis with accumulation of toxic viral structural proteins; cytolytic effects are visible microscopically and when destruction is extensive, effects can be seen with naked eye forming areas referred to as plaques in tissue cultures; in vivo, destruction of large numbers of cells results in impairment of tissue or organ structure & function

16 Host Cell Response Non-immunological = interferon production
Humoral - inhibits adsorption of virus to host cell surface (blocks receptors on virus) Cell mediated - acts against viral-specific proteins incorporated into host cell membrane; involves destruction of infected cell by sensitized T cells

17 Laboratory Techniques with Viruses
Viral isolation - require present of living cells Laboratory animals - suckling animals usually more susceptible than adult animals (e.g. suckling mice or guinea pigs) Embryonated eggs - chick or duck eggs used most often; viruses grow in embryo or on membranes

18 Laboratory Techniques with Viruses
Tissue culture Primary cell lines - prepared directly from tissue excised from humans or animals (e.g. primary monkey kidney = PMK cells) Continuous cell lines - cells that have been passaged indefinitely; are usually derived from malignant or premalignant cells (e.g. HeLa from human cervical carcinoma and HEp-2 from human laryngeal carcinoma

19 Laboratory Techniques with Viruses
Serological methods Patient's serum - show rising titer of antibodies to specific viruses Tissue culture - used to identify viruses that have been grown in the laboratory; have specific antisera for viruses; most often show neutralization of effect by antisera as indication of identity of virus

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