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Virology
OUTLINE
• introduction to viruses
– structure and classification
• basic virology
• clinical virology
VIROLOGY
• different structure
• different method of replication
• implications for
– diagnosis
– treatment
– prevention
(From Medical Microbiology, 4th ed., Murray, Rosenthal, Kobayashi & Pfaller, Mosby Inc., 2002, Fig. 65-1.)
Under attack!
Relative size of virusesRelative Size of Viruses
TEM column
Under vacuum
Specimen preparation
Electron Microscopy
• How is contrast achieved in the electron
microscope?
• Specimen is stained with an electron
dense material
– Some of the electrons passing through the
specimen are scattered by structures
stained with electron dense material
• Others pass through parts of the cell not
stained to form an image on a phosphorescent
screen
Growth on
artificial
media
Division by
binary
fission
Contain
DNA and
RNA
Contain
protein
synthesis
machinery
Contain
muramic
acid
Sensitive to
antibiotics
Bacteria often yes yes yes often yes
Viruses never no Either DNA
or RNA
no* no no
* The arenavirus family appears to ‘accidentally’ package ribosomes, but these appear to
play no role in protein synthesis.
CONSEQUENCES
• NO BROAD RANGE ANTIBIOTICS
• HEAVILY PARASITIC ON HOST CELL
• NEED TO LOOK FOR WEAK LINK
LIVING OR DEAD?
Definition of a Virus
A virus is a small, infectious, obligate
intracellular parasite, capable of
replicating itself in a host cell.
http://www.ncbi.nlm.nih.gov/genomes/VIRUSES/viruses.html
From Medical Microbiology, 5th ed., Murray, Rosenthal & Pfaller, Mosby Inc., 2005, Fig. 6-4.
Structures compared
From Medical Microbiology, 5th ed., Murray, Rosenthal & Pfaller, Mosby Inc., 2005, Fig. 6-1.
Basic virus structure
ENVELOPE
• OBTAINED BY BUDDING THROUGH A
CELLULAR MEMBRANE (except
poxviruses)
• POSSIBILITY OF EXITING CELL
WITHOUT KILLING IT
• CONTAINS AT LEAST ONE VIRALLY
CODED PROTEIN
Basic virus structure
VIRAL STRUCTURE – SOME
TERMINOLOGY
• virus particle = virion
• protein which coats the genome = capsid
• capsid usually symmetrical
• capsid + genome = nucleocapsid
• may have an envelope
Cubic Symmetry
http://www.tulane.edu/~dmsander/WWW/Video/Video.html
• Icosahedral pattern
• 20 faces
• 12 vertices
ICOSAHEDRAL SYMMETRY
3-FOLD5-FOLD 2-FOLD
12 PENTONS
240 HEXONS
Adenovirus
Icosahedron
• 60 identical subunits on the surface of an
icosahedron.
• To build a particle size adequate to
encapsidate viral genomes, viral shells are
ofen composed of multiples of 60 structural
units.
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ICOSAHEDRAL SYMMETRY
• Packaging sequences” on viral nucleic
acid are involved in assembly into virus particles.
• Icosahedral capsids are formed independently of
nucleic acid.
• “virus-like particles.”
26
SYMMETRY OF
NUCLEOCAPSID
• ICOSAHEDRAL
• HELICAL
TOBACCO MOSAIC VIRUS
nucleic acid
protein
adapted from:
Klug and Caspar Adv. Virus Res. 7:225
Helical symmetry
• Length controlled by nucleic acid
• Helix may be stiff or flexible
• It is not possible for “empty” helical particles
to form
COMPLEX SYMMETRY
POXVIRUS FAMILY
UNCONVENTIONAL AGENTS
• VIROIDS
– RNA only
– Small genome
– Do not code for protein
– So far, only known viroids are in plants
• hepatitis delta agent
- some viroid, some virus features
UNCONVENTIONAL AGENTS
• PRIONS
– protein only?
– do not contain any nucleic acid?
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laboratory animals
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Tissue culture
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tissue culture cells
epithelial epithelioid fibroblasticslides from CDC
Growth of virus on embryonated eggs
Davis, Duylbecco, Eisen, Ginsberg “Microbiology” 4th ed, J.B. Lippincott 1990, Fig. 48-1