Download Viruses, Viroids and Prions

Chapter 13
Viruses, Viroids and Prions
• Adolf Mayer, 1886
– tobacco mosaic disease (TMD) transmissible
• Dimitri Iwanowski, 1892
– Filtered sap still caused TMD
– contagious fluid or filterable agent
• Walter Reed,1901
– Yellow Fever
• Felix d’Herelle, 1917
– Bacteriophage
– Suggested phage therapy
• 1930’s, term virus introduced and
electron microscopy invented
• Wendell Stanley, 1935
– Isolated tobacco mosaic virus
[INSERT FIGURE 13.4]
• Viral Features
– Obligate intracellular pathogen
– Host range
• highly specific or generalists
– DNA or RNA
– Protein coat
– Surface proteins highly susceptible to mutations
– Cause synthesis of specialized structures to
transfer viral particles to other cells
• Virion
– complete, fully developed, infectious viral particle
– Living or non-living entities?????
Viral Classification
• Oldest system based on symptomology
• International Committee on Taxonomy of Viruses
(ICTV), 1966
– Describe viruses as elementary bio-systems
– Classified into orders, families, genera and species
– Over 1,500 officially recognized species
• 3 primary means of classification:
– Nucleic acid
– Replication strategy
– Morphology of protein coat (capsid)
Helical Viruses
Polyhedral Viruses
• Viral Envelope
–
–
–
–
Acquired from host cell
Phospholipids and proteins
Some glycoproteins are virally coded spikes
Often play role in host recognition
Critical Swine Flu prevention tip:
Don't DO this!
Complex Viruses
[INSERT FIGURE 13.5]
Viral Taxonomy
• Order –virales
• Family –viridae
• Genus – virus
• Species
– Common names
– Subspecies designated by a number
Viral Taxonomy
• Retroviridae– family
– Lentivirus – genus
• Human Immunodeficiency Virus– species
• Herpesviridae
– Simplexvirus
• Human herpesvirus 1, HHV 2, HHV 3
Isolation and Cultivation of Viruses
• Viruses must be grown
in living cells
– Cytopathic effects
• Animal viruses
may be grown in
living animals or
in embryonated
eggs
• Animal & plants viruses may be grown in cell cultures
– Primary cell lines
– Continuous cell lines (transformed cells )
Virus Identification
• Serological tests
– Detect antibodies against viruses in a patient
• Nucleic acids
– RFLPs
– PCR
Multiplication of Bacteriophages
• Lytic cycle
Phage causes lysis and
death of host cell
• Lysogenic cycle
Temperate phages
incorporate DNA into host
DNA (prophage)
Lytic Cycle
• Attachment
• Penetration
• Biosynthesis
• Maturation
• Release
Phage attaches by tail fibers to
host cell
Phage lysozyme opens cell wall,
tail sheath contracts to force tail
core and DNA into cell
Production of phage DNA
and proteins
Assembly of newly synthesized
phage particles
Phage lysozyme breaks cell wall
[INSERT FIGURE 13.8]
One-step Growth Curve
Lysogenic Cycle
• 3 Important results of lysogeny
– Immunity to re-infection
– Phage conversion
– Specialized transduction
Specialized Transduction
Prophage
gal gene
Bacterial DNA
1 Prophage exists in galactose-using host
(containing the gal gene).
Galactose-positive
donor cell
gal gene
2 Phage genome excises, carrying
with it the adjacent gal gene from
the host.
gal gene
3 Phage matures and cell lyses, releasing
phage carrying gal gene.
4 Phage infects a cell that cannot utilize
galactose (lacking gal gene).
Galactose-negative
recipient cell
5 Along with the prophage, the bacterial gal
gene becomes integrated into the new
host’s DNA.
6 Lysogenic cell can now metabolize
galactose.
Galactose-positive recombinant cell
Multiplication of Animal viruses
•
•
•
•
Attachment
Penetration
Uncoating
Biosynthesis
• Maturation
• Release
Viruses attaches to cell membrane
By endocytosis or fusion
By viral or host enzymes
Production of nucleic acid and
proteins
Nucleic acid and capsid proteins
assemble
By budding (enveloped viruses) or
rupture
• Attachment of animal viruses
– Chemical attraction
– No tails or tail fibers
– Glycoprotein spikes or other attachment molecules
• Replication of Animal Viruses
– Biosynthesis
• Each virus requires different strategy depending on
its nucleic acid
• DNA viruses often enter the nucleus
• RNA viruses typically replicate in cytoplasm
• Must consider:
– What serves as template for replication and how
mRNA is transcribed
Multiplication of DNA Virus
Papovavirus
1 Virion attaches to host cell
7 Virions are released
Host cell
DNA
Capsid
DNA
cell and its DNA is
uncoated
Cytoplasm
6 Virions mature
2 Virion penetrates
Capsid proteins
mRNA
5 Late translation;
capsid proteins
are synthesized
4 Late transcription;
DNA is replicated
3 Viral DNA penetrates host nucleus
Early transcription and translation;
enzymes are synthesized
Multiplication of RNA Virus
[INSERT FIGURE 13.13]
Multiplication of a Retrovirus
Capsid
Reverse
transcriptase
DNA
Virus
Two identical + stands of RNA
1 Retrovirus penetrates
host cell.
Host
cell
DNA of one of the host
cell’s chromosomes
5 Mature
retrovirus
leaves host
cell, acquiring
an envelope as
it buds out.
Reverse
transcriptase
Viral RNA
Identical
strands of
RNA
2 Virion penetrates
cell and its DNA is
uncoated
4 Transcription of the
Viral proteins
RNA
provirus may also occur,
producing RNA for new
retrovirus genomes and
RNA that codes for the
retrovirus capsid and
envelope proteins.
Provirus
3 The new viral DNA is
tranported into the host cell’s
nucleus and integrated as a
provirus. The provirus may
divide indefinitely with the
host cell DNA.
• Assembly and release of animal viruses
• Most DNA viruses assemble in and are released
from nucleus into cytosol
• Most RNA viruses develop solely in cytoplasm
• Enveloped viruses cause persistent infections
• Naked viruses are released by exocytosis or may
cause lysis and death of host cell
Viruses and Cancer
• Oncogenes transform normal cells into tumor cells
– Activated by mutagenic chemicals, radiation, viruses
– Causes increased growth, loss of contact inhibition
– Cells tend to be misshapen and exhibit chromosomal
abnormalities
•Oncoviruses
•Viral DNA integrated into
host DNA
•Induces tumors
Oncogenic Viruses
• Oncogenic DNA
Viruses
– Adenoviridae
– Herpesviridae
– Poxviridae
– Papovaviridae
– Hepadnaviridae
• Oncogenic RNA
viruses
– Retroviridae
• DNA
• HTLV 1
• HTLV 2
• Latent Viral Infections
– Virus remains dormant in asymptomatic host cell
for long periods
• Cold sores, shingles
• Persistent Viral Infections
– Disease progresses slowly over a long period,
generally fatal
• Subacute sclerosing panencephalitis
(measles virus)
• Plant Viruses
– Plant viruses
enter through
wounds or via
biting insects
– May be
transmitted in
pollen
• Viroids
– infectious naked
RNA
Potato Spindle Tuber Viroid
Prions
• Proteinaceous infectious particle
• Inherited and transmissible diseases
• Spongiform encephalopathies
– Sheep scrapie, Creutzfeldt-Jakob disease, GerstmannSträussler-Scheinker syndrome, fatal familial insomnia,
mad cow disease
PrPC, normal cellular prion protein
PrPSc, scrapie protein
[INSERT FIGURE 13.23]
scrapie proteins accumulate in brain cells forming large vacuoles