Viruses, Viroids, and Prions Chapter 13

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Viruses, Viroids, and Prions Chapter 13
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General Characteristicsof Viruses

• Viruses may be regarded as
• Complex aggregations of nonliving chemicals.
• Exceptionally simple living microbes.
• Viruses contain
• Either DNA or RNA (Single or Double strand)
• A protein coat
• Sometimes an envelope
• Viruses are obligatory intracellular parasites.
  They reproduce using the host cell's synthesizing
  machinery.

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Host Range

• Host Range
• 1. Host range Spectrum of host cells in which a
  virus can multiply
• 2. Most viruses infect only specific types of
  cells in one host species
• Polio virus - nerve cells
• Adenovirus - cells in upper Respiratory Tract
• Do not generally cross species barriers. Some
  viruses only infect
• plants
• invertebrates
• protists
• fungi
• bacteria (Bacteriophages)
• 3. Host range is determined by the specific
  Receptor attachment site on the host cell's
  surface and the availability of host cellular
  factors for viral multiplication.
• 4. Binding Sites on viral envelope must match
  Receptor Sites on Host cells

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Smallpox
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Viral Size

• 1. Viral size is ascertained by electron
  microscopy.
• 2. Viruses range from 20 nm (parvovirus) to
  14,000 nm (rabies virus) in length.

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Viral Structure Nucleic Acid

• Viral Structure
• A virion is a complete, fully developed viral
  particle composed of nucleic acid surrounded by a
  protein coat.
• Nucleic Acid
• 1. DNA or RNA (but never both)
• ss DNA
• ds DNA
• ss RNA
• ds RNA
• linear or circular, or divided into several
  separate segments (influenza virus).
• 2. The proportion of nucleic acid in relation to
  protein in viruses ranges from about 1 to about
  50.

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Capsid and Envelope

• 1. The protein coat surrounding the nucleic acid
  of a virus is called the capsid.
• 2. The capsid is composed of subunits capsomeres
  (single or several types of protein).
• 3. The capsid of some viruses is enclosed by an
  envelope (lipids, proteins, and carbohydrates).
• 4. Some envelopes are covered with
  carbohydrate-protein complexes (glycoproteins)
  called spikes (assist in attachment).

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General Morphology

• 1. Helical viruses (Ebola virus) resemble long
  rods and their capsids are hollow cylinders
  surrounding the nucleic acid.

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General Morphology

• 2. Polyhedral viruses
• (adenovirus, respiratory infections) are
  many-sided. Usually the capsid is an icosahedron
  (a polyhedron with 20 faces)

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General Morphology

• 3. Enveloped viruses Covered by an envelope and
  are roughly spherical but highly pleomorphic (two
  or more structural forms during a life cycle for
  example, smallpox virus).
• Enveloped helical viruses (for example, Influenza
  virus)
• Enveloped polyhedral (icosahedron) viruses (for
  example, Herpes virus).

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General Morphology

• 4. Complex viruses have complex structures. For
  example, many bacteriophages (or phages) have a
  polyhedral capsid (head) with a helical tail
  (sheath).

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Taxonomy of Viruses

• 1. Classification of viruses is based on
• Type of nucleic acid,
• Strategy for replication,
• Morphology.
• 2. Family names end with viridae such as
  Adenoviridae (adenoviruses)
• 3. Genus names end with -virus such as
  Influenzavirus (no specific epithets)
• 4. A viral species is a group of viruses sharing
  the same genetic information and ecological niche.

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Isolation, Cultivation, and Identification of
Viruses

• 1. Viruses must be grown in living cells.
• 2. The easiest viruses to grow are bacteriophages.

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Growth of Bacteriophages in the Laboratory

• The plaque method
• Mixes bacteriophages with host bacteria and
  nutrient agar.
• After several viral multiplication cycles, the
  bacteria in the area surrounding the original
  virus are destroyed the area of lysis is called
  a plaque.
• Each plaque originates with a single viral
  particle the concentration of viruses is given
  as plaque-forming units (PFUs).

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Viral Plaques
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Growth of Animal Viruses in the Laboratory

• 1. Cultivation of some animal viruses requires
  whole animals (mice, rabbits, guinea pigs).
• 2. Chicken Embryos (Eggs)
• used to be most common method to grow viruses
• Still used to produce many vaccines (Flu
  Vaccine)
• 3. Cell Cultures
• Most common method to grow viruses today

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Virus Cultivation

• Growth Chicken Embryos (Eggs)

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Viral Identification

• 1. Serological tests are used most often to
  identify viruses (antigen antibody reaction).
• 2. Viruses may be also identified by nucleic acid
  finger prints.

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Viral Multiplication

• 1. Viruses do not contain enzymes for energy
  production or protein synthesis.
• 2. For a virus to multiply, it must invade a host
  cell and direct the host's metabolic machinery to
  produce viral enzymes and components.

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Multiplication of Bacteriophages

• Reproduction through either a Lytic cycle or a
  Lysogenic cycle.
• Lytic cycle
• A phage causes the lysis and death of a host cell.

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Electron Micrograph of a T-even Bacteriophage
(Lytic) with a Contractile SheathA normal
bacteriophage B bacteriophage after
contraction of sheath
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Multiplication of Bacteriophages

• Lysogenic cycle
• Some viruses can either cause lysis or have their
  viral DNA incorporated as a prophage into the DNA
  of the host cell (lysogeny).
• Mutagens and/or spontaneous random events
  (recombination) can lead to excision of the
  prophage and initiation of the Lytic cycle.
• A lysogenic phage can transfer bacterial genes
  from one cell to another through transduction
• Some phage genes assist in virulence of bacteria
  Toxins of Corynebacterium diphtheriae, C.
  botulinum Vibrio cholerae.

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Bacteriophage Lambda A temperate or lysogenic
phage
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Multiplication of Bacteriophages - Continue

• Burst time The time from phage adsorption to
  release is called (20 to 40 minutes).
• Burst size The number of newly synthesized
  phages produced from a single infected cell (50
  to 200 or more viral particles).

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Animal Virus Replication(Enveloped
Nonenveloped viruses)

• 1. Attachment
• Binding Sites must match receptor sites on host
  cell
• 2. Penetration
• Endocytosis (Phagocytosis)
• Fusion (HIV viral envelope fuses with plasma
  membrane of the host cell to release capsid in
  the cytoplasm)
• 3. Uncoating
• Separation of the viral genome from the capsid

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Animal Virus Replication(non-enveloped virus)

• 4. Biosynthesis
• Viral genome Replication (DNA in the hosts
  nucleus and RNA in cytoplasm of hosts cell
  transcription translation)
• Capsid protein synthesis (in cytoplasm of hosts
  cell)
• 5. Assembly of virions
• Virus particles are assembled (in the hosts
  nucleus)
• 6. Release
• Lysis Nonenveloped viruses.
• Budding Enveloped viruses

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Retroviridae carry reverse transcriptase which
transcribes DNA from RNA.

• DNA ---------gt mRNA ------------gt Protein

SS or DS DNA virus Central Dogma
RNA -------gt DNA --------gt mRNA -------gt
Protein (RNA dependent DNA polymerase)
RNA reverse transcriptase viruses Retro
virus (i.e. HIV) Reverse of Central Dogma hence
Retro
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(No Transcript)
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HIV Life Cycle An Animation

• http//www.hopkins-aids.edu/hiv_lifecycle/hivcycle
  _txt.html

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Viruses and Cancer

• Chicken leukemia and chicken sarcoma (In early
  1900s transferred to healthy animals by cell-free
  filtrates)
• A cancer of connective or supportive tissue
  bone, cartilage, fat, muscle, and blood vessels.

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Viruses and Cancer Transformation of Normal
Cells into Tumor Cells

• 1. Activated oncogenes (cancer causing genes)
  transform normal cells into cancerous cells.
• 2. Tumors producing viruses are called oncogenic
  viruses.
• 3. Several DNA viruses (Epstein Barr virus,
  lymphoma may be Hodgkins disease?) and
  retroviruses (Human T-cell leukemia virus.) are
  oncogenic.

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Viruses and Cancer Transformation of Normal
Cells into Tumor Cells

• 4. The genetic material of oncogenic viruses
  becomes integrated into the host cell's DNA.
• 5. Transformed cells
• Lose contact inhibition
• Contact inhibition Normal cells will stop
  growing when they start to touch other cells and
  have filled up an area. Cancer cells do not stop
  growing when they reach other cells,
• Contain virus-specific antigens (suppression of
  membrane proteins that are essential for immune
  recognition and activation)
• tumor specific transplantation antigens.
• T antigen (virus induced Tumor antigen)
• Exhibit chromosomal abnormalities.
• Produce tumors when injected into susceptible
  animals.

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RNA Oncogenic Viruses

• The virus ability to produce tumors is related to
  the production of reverse transcriptase
• The (DS) DNA synthesized from the viral RNA
  becomes a provirus. Its integrated (integrase)
  into the host cell's DNA.
• It may contain oncogenes or promoters that turn
  oncogenes on.
• A provirus can remain latent, can produce
  viruses, or can induce cancer.

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Latent Viral Infections

• A latent viral infection
• The virus remains in the host cell for long
  periods without producing an infection.
• Examples
• Cold sores and Shingles
• An outbreak of rash or blisters on the skin that
  is caused by the same virus that causes chicken
  pox (varicella virus). The first sign of
  shingles is often burning or tingling pain.

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Persistent Viral Infections

• Persistent viral infections
• Disease processes that occur over a long period
  and are generally fatal, I.E. AIDS dementia
  complex
• A brain disorder that occurs in people with AIDS
  that causes the loss of cognitive capacity.
• Persistent viral infections are caused by
  conventional viruses viruses accumulate over a
  long period.

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Prions(Proteinaceous Infectious Particle)

• 1. Prions are infectious proteins first
  discovered in the 1980s.
• 2. Prion diseases involve degeneration of brain
  tissue
• Examples
• CJD (Creutzfeldt Jakob Disease) and Mad Cow
  Disease
• Scrapie is a fatal, degenerative disease
  affecting the central nervous system of sheep and
  goats. Its classified as transmissible
  spongiform encephalopathies (TSE). 
• 3. Prion diseases are due to an altered protein
• A mutation in the normal gene for PrPC (cellular
  prion protein) to the infectious form PrpSc
  (scrapie protein)
• Contact with an altered prion protein (scrapie
  protein).
• PrPc is a normal cell surface glycoprotein that
  is expressed in several tissue types (i.e.
  neurons and skeletal
• muscle). The normal physiological function of
  PrPc is not clear.

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Proposed mechanism of prion propagation
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Plant Viruses

• Plant viruses are DS DNA, SS or DS RNA.
• Enter plant hosts through wounds or with invasive
  parasites, such as nematodes, fungi or plant sap
  sucking insects.
• Some plant viruses also multiply in insect
  (vector) cells.
• Examples of diseases caused by
• Cauliflower mosaic virus
• Potato yellow dwarf virus

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Potato yellow dwarf
Cauliflower mosaic
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Viroids

• Viroids Infectious pieces of RNA (300 to 400
  nucleotide long), highly complementary circular
  molecules.
• The viroid RNA does not code for any proteins
• Reproduce by DNA-dependent RNA-polymerase.
• Viroids cause some plant diseases
• Potato spindle tuber viroid disease. Millions of
  dollars loss to growers.
• Hepatitis D in humans
• Called delta virus Small circular RNA virus
• The virus is an incomplete viral particle
  resembling a viroid 36 nm in diameter
• Only occurs in the presence of hepatitis B
  infection (needs Hepatitis B virus for
  reproduction).

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CDC Hepatitis D Virus (HDV) is a defective
single-stranded RNA virus that requires the
helper function of Hepatitis B Virus (HBV) to
replicate. HDV requires HBV for synthesis of
envelope protein composed of HB surface Antigen
(HBsAg), which is used to encapsulate the HDV
genome