General Virology-2

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General Virology-2

• What are viruses ?
• How do viruses replicate ?
• What effects do viruses have ?
• How do viruses change ?
• What are the consequences of change ?

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How do viruses replicate?

• Virus particles (virions) do not 'grow' or
  undergo division.
• Assembly of pre-formed components inside infected
  cells.
• Can only replicate within cellular environment
• Cell must be permissive for viral replication
• - permit ENTRY and permit REPLICATION

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How do viruses replicate?

• Different viruses exploit the host cell in
  different ways to replicate
• Infection of a cell may be
• productive, the cells are permissive for viral
  replication and virion progeny are released
• (cells may or may not be killed as a
  result)
• abortive, the cells are non permissive for
  replication and virion particles are not
  produced.
• Restrictive/latent, limited expression of viral
  genome/intermittent productive replication

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How do viruses replicate?
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1. Entry into cell
Entry into host cells includes the following
three steps A. Attachment Interaction between
cellular receptors and virus anti-receptors.
Entry binding of virus protein to cellular
receptor (Ig superfamily) induces conformational
change which delivers genome through membrane
pore into cytoplasm (translocation). B.
Penetration. C. Uncoating This can occur in the
cytoplasm or in the nucleus dependent on site of
replication.
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1. Entry into cell
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1. Entry into cell

• For a virus particle to infect a cell it must
  have on its surface a structure that is
  complementary to a receptor molecule on the cell
  surface.
• The virus attaches to specific receptors on the
  membrane. This process induces invagination of
  the membrane into a pit that is underlaid by the
  protein, clathrin.
• The clathrin-coated pit becomes a coated vesicle
  as endocytosis begins. Subsequent fusion of the
  vesicle with a cellular endosome occurs.
• The resulting lowering of the pH causes the viral
  surface to fuse with the endosomal membrane
  releasing the viral nucleocapsid into the
  cellular cytoplasm.

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2. Gene expression and genome replication
DNA viruses - nucleus use cellular RNA
polymerase and DNA polymerase (parvovirus) OR
virus-encoded (e.g. herpes encode DNA dependent
DNA pol) DNA viruses - cytoplasm encode own RNA
and DNA polymerases (poxviruses)
RNA viruses nucleus or cytoplasm encode own RNA
polymerase
Retroviruses (RNA) encode DNA polymerase
(RT) then use cellular RNA pol for mRNA and
genome production (nucleus)
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3A. Assembly

• All RNA viruses, except the orthomyxoviruses, are
  assembled in the cytoplasm.
• All DNA viruses, except the poxviruses, are
  assembled in the nucleus.
• Assembly is an automatic process triggered by
  high concentration of structural components
  associating with nucleic acid in which binding
  of structural proteins to the nucleic acid
  results in the formation of the nucleocapsid.

Adenovirus
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3B. Exit and Maturation
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Questions

• What are viruses ?
• How do viruses replicate ?
• What effects do viruses have ?
• How do viruses change ?
• What are the consequences of change ?

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What effects do viruses have ?
No effect (abortive/productive infection) Cell
damage/death Transformation
cell
cytopathic effect (CPE)
No effect Inapparent/subclinical
disease Local/systemic disease Cancer
uninfected
plaque
syncitium
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Effects of Viruses on Cells

• Mechanisms of Cell Damage
• Inhibition of host cell nucleic acid synthesis
• Inhibition of host cell transcription
• Inhibition of host cell protein synthesis
• Damage to cell membranes
• Induction of apoptosis

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Effects of Viruses on Cells

• Cell transformation - the introduction of
  inheritable changes in a cell causing changes in
  the growth phenotype
• - Alteration in cell morphology, cells
  immortalised, normal cells may become
  tumourigenic
• 15 human cancers associated with viral infection

In animals herpesviruses, retroviruses,
papillomaviruses
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Effects of viruses on host
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Effects of viruses on hosts

1. Cell/tissue destruction - can be direct/indirect

cerebellum
Feline panleucopenia Direct tissue destruction
by Parvovirus cerebellar hypoplasia
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Effects of viruses on hosts
2. virus-induced immunopathology or
immunosuppression
Feline infectious peritonitis (Coronavirus) Wet
or effusive form characterised by abdominal
distension due to peritoneal fluid
accumulations Immune complex formation results
in vascular damage
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Effects of viruses on hosts
3. Viral Oncogenesis
Mareks disease virus (Herpesviruses)
BPV-4 (Papillomavirus)
4. Inapparent infection undetected effects
(diagnosis, effect on fertility, transmission to
other susceptible animals) latent viruses,
potential for later disease
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Host defences against infection

• Physical skin, mucus, ciliated epithelium
• Lack of virus receptors on certain cell types
• pH (stomach acid)
• Immune system innate, humoral and cellular

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Host susceptibility to clinical disease

• - Age
• - Animal bread
• Nutritional Status
• Integrity of surface barriers
• Stress
• Concurrent infections
• Immune status