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Transcript
Lecture 6: Viruses, viroids, and prions
Edith Porter, M.D.
1
 Viruses
▪ General characteristics
▪ Viral structure
▪ Taxonomy
▪ Isolation, cultivation and identification
▪ Viruses and disease
 Viroids
 Prions
2
3
Virus is Latin for poison
Initially, viral disease described as disease that could
be transmitted with poisonous fluid that had been
passed through a “sterile” filter
 Acellular infectious agent


 Exceptionally complex aggregation of non-living
chemicals
OR
 Exceptionally simple living organism
Bacteria
Prions are
not viruses
5

Obligatory intracellular agents
 Require a cellular host for proliferation
 Multiply inside living cells by using entirely the synthesizing
machinery of the cell
 Cause the synthesis of specialized structures that can transfer
the viral nucleic acid to other cells






Most viruses infect only specific types of cells
in one host
Host range is determined by specific host attachment
sites and cellular factors
Contain single type of nucleic acid (DNA or RNA)
Contain a protein coat
Some are enclosed by an envelope
Some viruses have spikes

Contain a single type of nucleic acid
 Either DNA or RNA
 Single or double stranded

Protein coat surrounding nucleic
acid






Capsid
Composed of capsomer subunits
Protects
Vehicle for transmission
May contain a very limited number
of enzymes
Virion: complete virus with nucleic
acid and protein coat

Polyhedral (spherical,
icosahedral)

Helical (filamentous)

Complex

Spikes
 Glycoproteins projecting
from surface
 Can clump cells
▪ Hemagglutination

Envelopes
 Originate mainly from host
membranes
 Lipid, protein, carbohydrate
 Some virus encoded
proteins
Based on nucleic acid composition, replication mode,
morphology
 Family names end in –viridae (Herpesviridae)
 Genus names end in –virus (Herpesvirus)
 Viral species: A group of viruses sharing the same genetic
information and ecological niche (host). Common names are
used for species (Herpes simplexvirus)
 Subspecies are designated by a number (Herpes simplexvirus 2)
 Often abbreviated names

 HSV
 HIV
 CMV


In principle, any cell can be infected by a virus
A particular virus can infect only a specific host cell
type (receptor mediated entry)
 Prokaryotic cells
Mastadenovirus
▪ Bacterial viruses (phages)
▪ Archaeal viruses
 Eukaryotic cells
▪
▪
▪
▪
▪
▪
Fungal cells
Algae
Protozoa
Plant cell viruses
Insect cell viruses
Animal viruses
Fits only to specific structures
(receptors) on the host cell


Need a living host cell
Bacteriophages
 Bacteria

Plant virus
 Plant cells

Animal viruses
 Living animal
 Embryonated eggs
▪ Large scale production
 Cell culture
▪ diagnostics

Virus induced changes of
eukaryotic cell morphology
 Cell rounding
 Cell aggregation
 Inclusion bodies
 Cell fusion
 Transformation
▪ Continous growth of eukaryotic
cell

Can be used for diagnostic
Normal
Cell rounding

Cytopathic effects
 Monkey kidney cells
 Foreskin cells
 Fibroblasts
Hemagglutination
Serology (look for patient antibodies)
PCR (polymerase chain reaction, detects virus
specific nucleic acid sequences)
 RFLP (restriction fragment polymorphism)




Electron microscope
 Count

Plaque Assay
 Bacterial lawn
 Add virus
 Add agar on top to immobilize
virus
 Incubate
 Count plaques
▪ lack of bacterial growth where 1
virus had been
Eclipse is the period
immediately after
penetration during
which not a single
intact virus is present
 In vitro, no new host
cells are provided and
number of virions
decrease over time



V
Typically double stranded
DNA viruses
Lytic cycle
V
 Rapid large scale production of
V V
V VV
viruses
 Host cell lysis and death

V
V
V V
DEAD
Lysogenic cycle
 Host cell survives
 Viral genome incorporated
into host cell genome
 Replication with host cell
 No active virion production
V
V
V
V





Attachment
Penetration
Biosynthesis
Maturation and assembly
Host lysis and virion release
V
V
V V
V VV
V V
V V V
DEAD
V



Attachment
Penetration
Phage DNA integrates into bacterial host
genome by recombination
V
V
 Virus now: prophage
 Host cell: lysogenic bacterium
 Lysogenic conversion: bacterium produces virus
encoded proteins
▪ Prevent superinfection with similar phage
▪ Some are toxins (e.g. diphteria toxin by C. diphteriae)

Switch to lytic cycle
 can be induced by UV light
 Specialized transduction: accidentally, bacterial host
DNA is cut out too
V
V


Virus serves as vector for bacterial DNA
During virus assembly a segment of bacterial
DNA is accidentally packed into virus capsids
 Specialized transduction: a segment of bacterial
DNA along with the proper viral DNA
 Generalized transduction: only bacterial DNA is
packaged into the capsid
23
24




DNA or RNA viruses
Single or double stranded
Negative or positive sense
Unique viral biosynthesis pathways
 RNA viruses require enzymes not present in
eukaryotic cells




Attachment
Entry
Uncoating
Biosynthesis
 Early genes for replication
 Late genes for structural
elements


Assembly (maturation)
Release
 Host rupture: non-enveloped
viruses
 Budding: enveloped viruses
27
28



RNA viruses
Include HIV
Carry reverse transcriptase
 RNA-dependent DNA polymerase
 Synthesize DNA from RNA
 Used in molecular biology (RT-PCR)
30

Acute Infection
 Unspecific: fever, muscle and joint aches
 Specific: depend on target host cell

Latent Infections
 Virus retreats in host cells
▪ Herpesviridae in neurons (fever blisters)

Persistent Infections
 Slow virus disease
http://pathcuric1.swmed.edu/PathDemo/gbp
3/gbp340.jpg
 Gradual increase of symptoms
▪ Subacute sclerosing panenecephalitis after measles infection

Cancer
 Chicken leukemia virus, Epstein Barr virus (lymphoma), HPV (cervix
carcinoma) HBV (liver cancer)

Caused by various virus
genera




Conjunctivitis
Diarrhea
Encephalitis
“Flu”
▪ Influenza
▪ SARS
▪ Avian flu
 Hepatitis

Diseases with virus
specific symptoms




Measles
Rubella
Herpes
AIDS
RNA only
Short piece of naked RNA
RNA does not code for
protein
 Similarities between introns
and viroids
 Often found in plant
diseases




Protein only
 Proteinaceous infectious particle
 Infectivity can be reduced with protease treatment
 Infects central nervous system
Normal protein variant exists (PrPc)
Prion protein (PrPsc) induces conformation change of
normal variant and aggregation
 Snow ball effect
 Damage in central nervous system due to loss of cell
function and inflammatory host response
 Neurological disease


 Mad cow disease (with limited human transmission)
 Scrapie
 Creutzfeldt-Jakob disease
35

Viruses
 Acellular, requires a host cell to mulitply
 Protein capsid and 1 type of nucleic acid (RNA or DNA)
 Spherical, helical and complex structure
 Can have envelopes and carry a few enzymes
 Lytic and lysogenic multiplication in bacteria
 Uncoating and budding is part of animal virus multiplication

Viroids
 RNA only
 Plant diseases

Prions
 Protein only
 Neurological diseases