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.

24

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?

36

laboratory animals

36

37

Tissue culture

38

39

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