The Viruses: Introduction and General Characteristics

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Chapter 16

• The Viruses Introduction and General
  Characteristics

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General Properties of Viruses

• virion
• complete virus particle
• consists of ?1 molecule of DNA or RNA enclosed in
  coat of protein
• may have additional layers
• cannot reproduce independent of living cells nor
  carry out cell division as procaryotes and
  eucaryotes do
• Obligate intracellular parasites

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Generalized Structure of Viruses
Figure 16.1
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The Structure of Viruses

• virion size range is 10-400 nm in diameter with
  most viruses too small to be seen with the light
  microscope
• all virions contain a nucleocapsid which is
  composed of nucleic acid (DNA or RNA) and a
  protein coat (capsid)
• some viruses consist only of a nucleocapsid,
  others have additional components
• envelopes
• virions having envelopes enveloped viruses
• virions lacking envelopes naked viruses,
  non-envelope

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Capsids

• large macromolecular structures which serve as
  protein coat of virus
• protect viral genetic material and aids in its
  transfer between host cells
• made of protein subunits called protomers

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Helical Capsids

• shaped like hollow tubes with protein walls

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Tobacco Mosaic Virus Structure
Figure 16.3
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Influenza Virus an Enveloped Virus with a
Helical Nucleocapsid
Figure 16.4
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Icosahedral Capsids

• an icosahedron is a regular polyhedron with 20
  equilateral faces and 12 vertices
• it is one of natures favorite shapes
• capsomers
• ring or knob-shaped units made of 5 or 6 protomers

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Figure 16.5
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Figure 16.6
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Figure 16.7
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Figure 16.8
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Figure 16.9
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Viral Envelopes and Enzymes

• many viruses are bound by an outer, flexible,
  membranous layer called the envelope
• in eucaryotic viruses some envelope proteins,
  which are viral encoded, may project from the
  envelope surface as spikes or peplomers.

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Figure 16.10
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Virion Enzymes

• it was first erroneously thought that all
  virions lacked enzymes
• now known a variety of virions have enzymes
• some are associated with the envelope or capsid
  but most are within the capsid

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Viral Genome Acids

• A virus may have single or double stranded DNA or
  RNA
• the size of the nucleic acid also varies from
  virus to virus
• genomes can be linear or circular

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Figure 16.11
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Generalized Illustration of Virus Reproduction
Figure 16.12
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The Cultivation of Viruses

• requires inoculation of appropriate living host

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Hosts for animal viruses

• suitable animals
• embryonated eggs
• tissue (cell) cultures
• monolayers of animal cells
• plaques
• localized area of cellular destruction and lysis
• cytopathic effects
• microscopic or macroscopic degenerative changes
  or abnormalities in host cells and tissues

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Figure 16.13
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Figure 16.14
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Chapter 17

• The Viruses Bacteriophages

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Virulent Double-Stranded DNA PhagesT-even Phages
of E. coli

• lytic cycle
• phage life cycle that culminates with host cell
  bursting, releasing virions

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Life Cycle of dsDNA T4 Phage of E. coli

• adsorption to specific receptor site
• penetration of the cell wall
• insertion of the viral nucleic acid into the host
  cell
• transcription ? early mRNAm (before DNA is
  synthesizexd proteins enzymes needed to take
  over the cell)
• translation of early mRNA resulting in production
  of protein factors and enzymes involved in phage
  DNA synthesis

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Phage T4 Life Cycle continued

• transcription ? late mRNA
• translation of late mRNA resulting in synthesis
  of capsid proteins, proteins required for phage
  assembly and proteins required for cell lysis and
  phage release
• cell lysis and phage release

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Maturation assembly
Figure 17.3
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Adsorption and Penetration

• receptor sites
• specific surface structures on host to which
  viruses attach
• specific for each virus
• can be proteins, lipopolysaccharides,

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Figure 17.4
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Figure 17.5
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Synthesis of Phage Nucleic Acids and Proteins

• most double-stranded DNA viruses
• use their DNA genome as a template for mRNA
  synthesis
• the mRNA is translated to produce viral proteins

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Replication Strategy Used by Double-Stranded DNA
Viruses
Figure 17.6
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Map of the T4 Genome
early genes
genes with related functions are
usually found clustered together
late genes
Figure 17.7
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Assembly of Phage Particles

• complex self-assembly process
• involves viral proteins as well as some host cell
  factors

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Figure 17.11
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Release of Phage Particles

• in T4 - E. coli system, 150 viral particles are
  released
• two proteins are involved in process
• T4 lysozyme attacks the E. coli cell wall
• holin creates holes in the E. coli plasma membrane

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Temperate Bacteriophages and Lysogeny

• temperate phages have two reproductive options
• reproduce lytically as virulent phages do
• remain within host cell without destroying it
• done by many temperate phages by integration of
  their genome with the host genome in a
  relationship called lysogeny

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Lysogeny

• prophage
• integrated phage genome
• lysogens (lysogenic bacteria)
• infected bacterial host
• temperate phages
• phages able to establish lysogeny

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Distinctive characteristics of Lysogenic Bacteria

• they are immune to superinfection
• under appropriate conditions they will lyse and
  release phage particles
• this occurs when conditions in the cell cause the
  prophage to initiate synthesis of new phage
  particles, a process called induction

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Focus on lambda phage

• double-stranded DNA phage
• linear genome with cohesive ends
• circularizes upon entry into host

Figure 17.17
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Lambda Phage DNA

• the DNA contains 12 base single-stranded cohesive
  ends
• circularization results from complementary base
  pairing

Figure 17.18
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The Genome of Phage Lambda (l)
Figure 17.19
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Infection by Lambda Phage

• Two proteins appear after infection
• the lambda repressor
• product of cI gene (blocks lytic)
• blocks transcription of the cro gene and other
  genes required for the lytic cycle
• Cro protein (blocks lysogenic)
• product of cro gene
• inhibits transcription of the lambda repressor
  gene

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If Lambda Repressor Wins Race with the Cro
protein

• lysogeny is established
• lambda genome is integrated into the host genome
  in a reaction catalyzed by the enzyme, integrase

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Attachment site On the chromosome
Figure 17.22
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Induction

• triggered by drop in levels of lambda repressor
• caused by exposure to UV light and chemicals that
  cause DNA damage

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Fig. 13.34
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Chapter 18

• Eucaryotic Viruses and Other Acellular Infectious
  Agents

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Reproduction of Animal Viruses

• adsorption
• penetration and uncoating
• replication of virus nucleic acids
• synthesis and assembly of virions
• virion release

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Adsorption

• virions attach to host cells displaying the
  proper receptor

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Penetration and Uncoating

• one of two mechanisms used by most viruses
• fusion of envelope with host cell membrane
• endocytosis
• in some cases only nucleic acid enters host cell

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Fusion with host membrane
Figure 18.4 (a)
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Endocytosis enveloped virus
Figure 18.4 (b)
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• Uncoating envelope and capsid are broken down.
  Genetic material is released.

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Endocytosis naked virus
Figure 18.4 (c)
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Genome Replication and Transcription in DNA
Viruses

• early genes
• encode proteins involved in take over of host and
  in synthesis of viral DNA and RNA
• viral DNA replication
• usually occurs in nucleus
• early mRNA synthesis
• usually by host RNA polymerase

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e.g., herpes simplex virus I
uses host RNA polymerase for synthesis of
viral mRNA
uses virus- encoded DNA polymerase
for replication of genome
Figure 18.6
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• Retrovirus (HIV)
• RNA genetic material
• Reverse transcriptase uses viral RNA template
  to make viral DNA

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budding
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Assembly of Virus Capsids

• late genes direct capsid protein synthesis which
  spontaneously self-assemble to form the capsid
• during icosahedral virus assembly empty
  procapsids form first, nucleic acid are then
  inserted
• assembly of envelope viruses (maturation)
• in most cases, similar to assembly of naked
  viruses

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Virion Release

• all viral envelopes are derived from host cell
  membranes in multistep process
• naked viruses
• usually by lysis of host cell
• envelope viruses (budding)
• formation of envelope and release usually occur
  concurrently
• virus-encoded proteins incorporated into host
  membrane
• nucleocapsid buds outward and is surrounded by
  modified host membrane

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Release of influenza virus by budding
Figure 18.11
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HIV release by budding
Figure 18.12 (a)
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Figure 18.12 (b)
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Cytocidal Infections and Cell Damage

• cytocidal infection
• infection that results in cell death

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Mechanisms of host cell damage and cell death

• inhibition of host DNA, RNA, and protein
  synthesis
• lysosome damage
• causes release of hydrolytic enzymes into cell
• alteration of plasma membrane
• can lead to attack of host cell by immune system
• can lead to cell fusion, forming syncytium
  multinucleated cells

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Other mechanisms

• toxicity from high concentrations of viral
  proteins
• formation of inclusion bodies
• can disrupt cell structure
• chromosomal disruptions
• transformation of host cell into malignant cell

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Latent viral infection

• Herpes simplex virus
• Dormant nerve cells, activated under certain
  conditions epithelial cells cold sores
• Herpes simplex virus 1 oral herpes
• Infancy - direct contact
• Activated by fever, sunburn, stress

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Herpes Simplex Virus 2

• Genital herpes
• Vesicles in the area
• Burning, difficulty walking
• acyclovir

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Viruses and cancer

• Nucleated cells have proto-oncogenes
• Control (regulate) cell growth
• Code for proteins regulate cell growth
• Mutation abnormal proteins
• Loss of control uncontrolled proliferation of
  the cell with mutation - cancer

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Mutations

• Chemicals
• UV light
• Viruses
• Epstein-Barr virus DNA virus
• Dormant in some B lymphocytes
• Transmitted in saliva infectious mononucleosis

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Epstein-Barr virus

• DNA virus
• Dormant in some B-lymphocytes
• Transmitted in saliva
• Infectious mononucleosis

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Burkitts Lymphoma

• Common childhood cancer in Africa
• Average age 7 malaria is common
• EBV and Plasmodium cause mutation in
• c-myc gene proto-oncogene
• Loss of control of cell growth
• Uncontrolled proliferation
• Leads to cancer jaw bones

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Prions

• Proteinaceous infectious particles proteins
• Scrapie sheep
• Scrape themselves against fences
• Become paralyzed and die
• Mad cow disease bovine spongiform
  encephalopathy (BSE) sponge like degeneration
  of the brain.
• Shake, shiver

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Creutzfeldt jakob disease

• Occurs in certain families hereditary
• Transmitted by contaminated hamburgers
• Dementia die within a year

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viroids

• Naked piece of RNA
• Plant pathogen
• Potato spindle tuber viroid
• Damage to potato plants
• Evolved from introns

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Prions Proteinaceous Infectious Particle

• examples of degenerative diseases in animals
  caused by prions
• scrapie
• bovine spongiform encephalopathy (BSE) or mad cow
  disease
• Creutzfeldt-Jakob disease (CJD) and varient CJD
  (vCJD)
• kuru

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Current Model of Disease Production by Prions

• PrPC (prion protein) is present in normal form
  in host and abnormal form of prion protein is
  PrPSc
• entry of PrPSc into animal brain causes PrPC
  protein to change its conformation to abnormal
  form.
• the newly produced PrPSc molecules then convert
  more normal molecules to the abnormal form
• interactions between PrPSc and PrPC may result
  in the crosslinking of PrPC molecules resulting
  in neuron loss

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What about Mad Cow Disease?

• prions cause bovine spongiform encephalopathy
  (BSE or mad cow disease)
• epidemic proportions in England in 1990s
• initially spread because cows were fed meal made
  from all parts (including brain tissue) of
  infected cattle

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Variant Creutzfeldt-Jakob (vCJD) v. CJD

• difference in diseases is origin
• eating meat from BSE infected cattle can cause
  variant Creutzfeldt-Jakob (vCJD) in humans
• CJD is caused by spontaneous mutation of the gene
  that codes the prion protein
• all prion caused diseases
• have no effective treatment
• result in progressive degeneration of the brain
  and eventual death