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An Introduction to the Viruses
Chapter 6
The Search for the Elusive Virus
• ______________ postulated that rabies was
caused by a virus (1884)
• Ivanovski and Beijerinck showed a disease in
tobacco was caused by a virus (1890s)
• 1950s virology was a multifaceted discipline
– Viruses: noncellular particles with a definite size,
shape, and chemical composition
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The Position of Viruses in the
Biological Spectrum
• There is no universal agreement on how
and when viruses originated
• Viruses are considered the most abundant
microbes on earth
• Viruses played a role in evolution of
Bacteria, Archaea, and Eukarya
• Viruses are obligate intracellular parasites
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
Size of viruses
Naming viruses
Classified based on structures, size, nucleic acids, host
species, target cells.
• 3 orders, 63 families, and 263 genera of viruses
• Family name ends in -viridae
• Genus name ends in -virus, Simplexvirus, Hantavirus,
Enterovirus
• Name of genus or family begins with description of
virus
–
–
–
–
appearance: togavirus, coronavirus
place collected: adenovirus, hantavirus
effect on host: lentivirus
acronymns: picornavirus; (arbovirus)
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Examples
• Family – Herpesviridae
• Genus – Varicellovirus
• Common name – chickenpox virus
• Disease - chickenpox
• Family – Herpesviridae
• Genus – Simplexvirus
• Common name – herpes virus (Herpes
simplex virus I (HSV-I)
• Disease – fever blisters, cold sores
terminology
• Virus = virus particle
• ___________– fully formed, virulent,
extracellular
• ___________– host cell is lysed
(broken) to release virions
• ___________– viruses are inactive
(latent stage) and host cell isn’t lysed
(virus may be integrated within host
genome)
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Viral structure
• ___________ (with spikes/receptors;
13/20 – derived from host cell) – may not
be present
• ___________ (morphologies: helical,
icosohedral, complex)
• Nucleic acid (DNA/RNA; ds or ss)
• Matrix proteins (some enzymes)
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capsids
• Nearly all viruses have capsids- protein
coats that enclose & protect their
nucleic acid
• Each capsid is constructed from
identical subunits called capsomers
made of protein – can self-assemble
• ___________= capsid & nucleic acid
• 2 types (based on shape):
– helical
– icosahedral
Envelope
• If present, made primarily of lipids
• ______________________ ; (ER,
nuclear envelope, cell membrane-budding)
• May be embedded with spikes for host
recognition/binding
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4 morphological types
• Due to capsule shape and/or whether it’s
enveloped
1. Helical
2. Icosahedral
3. Enveloped (with Hel. or Icos. capsid)
4. complex
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Morphological types
1. Helical capsid
• Rod-shaped
•
•
capsomers
Coil around hollow
center
Nucleic acid is kept
inside – wound-up
within tube
(nucleocapsid)
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Morphological types
Helical – capsid surrounds DNA like hollow tube
Ex: TMV, influenza, measles, rabies (last 3 are
enveloped)
Morphological types
Tobacco Mosiac Virus
Influenza virus
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Morphological types
2. icosahedral
• 20-sided with 12
•
•
•
corners
Vary in the number of
capsomers
Each capsomer may be
made of 1 or several
proteins
Some are enveloped
Figure 6.7
Figure 6.8
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Morphological types
Human papilloma virus
Adenovirus
Icosahedral – 3D,
20 sided
Herpesvirus
Morphological types
3. envelope
• Naked viruses
– Capsid proteins exposed to environment
– Released from cells as cells ____________________
– Not a good pathogenic feature should keep host alive
• Enveloped viruses
– Covered with a lipid bilayer
– ______________________
– Host cell keeps producing virus much longer sometimes
for extended periods
– Can bud off cell – thereby not destroying (lysing) it
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Morphological types
Enveloped vs. naked viruses
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Morphological types
4. Complex viruses
• Have additional or special structures
• Examples:
• ___________– lack normal capsid –
instead, layers of lipoprotiens and fibrils
on surface
• ___________viruses have a polyhedral
head, helical tail and fibers for
attachment.
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Morphological types
Fig 6.9a,c
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Nucleic Acids
• Viral genome – either DNA or RNA but
never both
• Carries genes necessary to invade host
cell and redirect cell’s activity to make
new viruses
• Number of genes varies for each type
of virus – few to hundreds
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Nucleic Acids
• DNA viruses
– Usually double stranded (ds) but may be single
stranded (ss)
– Circular or linear
• RNA viruses
– Usually single stranded, may be double
stranded, may be segmented into separate RNA
pieces
– ssRNA genomes ready for immediate translation
are positive-sense RNA
– ssRNA genomes that must be converted into
proper form are negative-sense RNA
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Enzymes important to replication
• Pre-formed enzymes may be
present
– ___________– DNA or RNA
– ___________– copy RNA
– ______________________–
synthesis of DNA from RNA (AIDS
virus)
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Viral life cycles
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Life cycle
Host range
• Spectrum of cells a virus can infect
– cell has to have a specific structure (receptor) on its
surface for viral attachment
– cell has to contain all of the enzymes and materials
needed to produce new virions
• May be one species or many
– HIV (only humans) vs rabies (many animals)
– Bacteriophages – tend to be very specific
• May be one tissue or many within a host
– Hepatitis (liver) vs polio (intestinal & nerve cells)
DNA replication
in viruses
* Uses host machinery!*
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animal virus replication (life cycle)
Viral Multiplication – animal viruses
1. ___________– binding of virus to specific
molecule on host cell
2. ___________– genome enters host cell
3. ___________– the viral nucleic acid is released
from the capsid
4. ___________– viral components are produced
5. ___________– new viral particles are
constructed
6. ___________– assembled viruses are released
by budding (exocytosis) or cell lysis
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1. Adsorption and Host Range
• Virus coincidentally collides with a susceptible
host cell and adsorbs specifically to receptor
sites on the cell membrane
• Spectrum of cells a virus can infect – host
range
– ___________– human liver cells
– ___________– primate intestinal and nerve
cells
– ___________– various cells of many mammals
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1. Adsorption to host cell membrane
(a) Coronavirus with envelope spikes
(b) adenovirus (naked capsid) with surface capsid spikes
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Entry: (2. penetration & 3. uncoating)
Entry (viruses with envelopes)
• first must attach to cell membrane using receptors -usually specific for host AND cell type
• After adsorption  _________ of membranes – (like
two soap bubbles)
• leaves the capsid free in the cytoplasm
Entry (viruses without envelopes)
• first must attach using receptors (specific)
• if a match, then engulfment -- ___________
• capsid then in the cytoplasm but within a vacuole
• virus must uncoat without the genes being degraded
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Figure 6.13
Entry of viruses into cells (penetration and uncoating)
• Endocytosis and engulfment of herpesvirus;
• Fusion of cell membrane with viral envelope (mumps)
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Synthesis: Replication and Protein
Production
• Varies depending on whether the virus is a
DNA or RNA virus
• DNA viruses generally are replicated and
assembled in the ___________
• RNA viruses generally are replicated and
assembled in the ___________
– Positive-sense RNA contain the message for
translation
– Negative-sense RNA must be converted into
positive-sense message
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Duplication and synthesis: viral
replication (more details in Ch. 9)
Transport of DNA/RNA to nucleus
• most viruses must get genes to nucleus to survive
• some integrate into host DNA (leads to latency)
– may require conversion of RNA copy to DNA
• some remain independent chromosomes
Viral replication
• some do direct copies of DNA->DNA or RNA->RNA
• others use "reverse transcriptase" to do RNA->DNA
conversion
– then DNA->RNA using HOST enzymes
– timing is important -- some replicate only late in the cycle, after
all proteins are made
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5. Assembly: Filling the capsid
• Capsid proteins made in cytoplasm
• DNA or RNA gets fills empty capsids
• final modifications to capsid
– to plug any holes from DNA/RNA entry
– to mature the outer proteins
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6. Release
• Two ways assembled viruses leave host cell:
1. ___________– exocytosis; nucleocapsid binds
to membrane which pinches off and sheds the
viruses gradually; cell is not immediately
destroyed
2. ___________– nonenveloped and complex
viruses released when cell dies and ruptures
• Number of viruses released is variable
– 3,000-4,000 released by poxvirus
– >100,000 released by poliovirus
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Viral budding – picking up cell membrane upon exit
Budding of
parainfluenza
virus
Budding of HIV
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Damage to Host Cell
Cytopathic effects - virus-induced damage
to cells
1. Changes in size and shape
2. Cytoplasmic inclusion bodies
3. Inclusion bodies
4. Cells fuse to form multinucleated cells
5. Cell lysis
6. Alter DNA
7. Transform cells into cancerous cells
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Figure 6.16
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Persistent infections with viruses
• Persistent infections - cell harbors the
virus and is not immediately lysed
• Can last weeks or host’s lifetime; several
can periodically reactivate –
______________________
– Measles virus – may remain hidden in brain
cells for many years
– Herpes simplex virus – cold sores and genital
herpes
– Herpes zoster virus – chickenpox and shingles
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Persistent infections with viruses
• Some animal viruses permanently alter genetic
material  ________________
• Transformed cells have increased rate of growth,
altered chromosomes, and can become “immortal”
 tumors (cancerous or noncancerous growths)
• Mammalian viruses capable of initiating tumors are
called _________________
– Papillomavirus – genital warts/cervical cancer
– Epstein-Barr virus – Burkitt’s lymphoma
– HBV and liver cancer
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Multiplication Cycle in Bacteriophages
• ___________– bacterial viruses (phages)
• Most widely studied are those that infect
Escherichia coli – complex structure, DNA
• Multiplication goes through similar stages as animal
viruses
• Only the nucleic acid enters the cytoplasm -
•
uncoating is not necessary
Release is a result of cell lysis induced by viral
enzymes and accumulation of viruses - lytic cycle
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6 Steps in Phage Replication
1. Adsorption – binding of virus to specific
2.
3.
4.
5.
6.
molecule on host cell
Penetration – genome enters host cell
Replication – viral components produced
Assembly – viral components assembled
Maturation – completion of viral formation
Release – viruses leave cell to infect other
cells
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Figure 6.17
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Figure 6.18
Figure 6.19
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Lysogeny: The Silent Virus Infection
• Not all phages complete the lytic cycle
• Some DNA phages (temperate phages), undergo
•
•
•
adsorption and penetration but don’t replicate
The viral genome inserts into bacterial genome and
becomes an inactive ___________– the cell is not
lysed
Prophage is retained and copied during normal cell
division  transfer of temperate phage genome to all
host cell progeny – ___________
Induction can occur resulting in activation of
lysogenic prophage followed by viral replication and
cell lysis
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Figure 6.17
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Lysogeny
• Lysogeny results in the spread of the virus
without ______________________
• Phage genes in the bacterial chromosome can
cause the production of toxins or enzymes
that cause pathology – lysogenic
conversion
– Corynebacterium diphtheriae
– Vibrio cholerae
– Clostridium botulinum
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Growing animal viruses
Viral Culture
Obligate intracellular parasites that require appropriate
cells to replicate
1. live animals (dependent on host
specificity)
2. bird embryos – chicken, duck; intact,
self-supporting unit, sterile, selfnourished
3. cell culture – can be used to cultivate but
also to test toxic (ex. Hemolytic) effects
Figure 6.20
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Figure 6.21
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Medical Importance of Viruses
• Viruses are the most common cause of acute
infections
• Several billion viral infections per year
• Some viruses have high mortality rates
• Possible connection of viruses to chronic
afflictions of unknown cause
• Viruses are major participants in the earth’s
ecosystem
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Detection of Animal Viral Infections
• More difficult than other agents
• Consider overall clinical picture
• Take appropriate sample
– Infect cell culture – look for characteristic
cytopathic effects
– Screen for parts of the virus
– Screen for immune response to virus
(antibodies)
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diagnosis
Treatment of viral infections
• Antiviral drugs
• Target viral replication – but usually lots of
side effects (affects host cells too)
• Some drugs target virus-specific enzymes
Best bet…get ___________and avoid
infection
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Clinically-important viruses (just a few examples!)
HepC
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Important viruses you should know…
• Smallpox (variola major, minor) – complex virus; inclusions
• Herpesviridae – (herpes; chicken pox – varicella zoster);
•
•
•
•
•
•
•
•
•
chronic latent state  reactivated; nuclear inclusions
HPV – can transform cells; warts  cervical cancer
Hepatovirus (A, B, C) – see table
Polio – enterovirus – enteric (oral vaccine)
Cold (Rhinovirus) – antibiotics ineffective! It’s a virus!!
West Nile – is a flavivirus; spread by moquitoes; bird is
reservoir
SARS – coronavirus (like the virus that causes bronchitis);
prominent spikes on envelope
influenza – Flu; Type A is the one you’ve had;
Rotavirus – viral food poisoning; vomiting and diarrhea –
sometimes concurrently!!
HIV – retrovirus; latency; (see slide)
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Herpesviridae
• Examples:
– _______________ (cold sores); 2 (genital herpes)
– ______________________ (chicken pox)
• Have chronic latent phase in nerve cells
• Reactivated by various stimuli:
– Foods
– Sunlight
– Stress
• Chicken pox  reappears as “___________”
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Hepatoviruses and Hepatitis
Organism
Hep A
Hep B
Hep C
Virus
Non-enveloped;
ssRNA
Enveloped; ss and
dsDNA
RNA (flaviviridae)
Disease
Short-term
hepatitis
Chronic infection (6%),
liver cancer, death
Chronic infection (7585%) liver disease
very common, cancer,
death
Transmission
Fecal/oral
Blood/fluid contact (IV,
sex, tattoos); vertical
Blood/fluid contact
(IV, sex, tattoos);
vertical
Treatment
Immune globulin Interferon, nucleoside
analogs
Interferon or ribavirin
Prevention
Vaccine
Vaccine
No vaccine; avoid
exposure
Special notes
Resolves (selflimiting); avoid
aspirin, alcohol
Survives in infected
blood for days, freezing
“silent epidemic; 4M
people, 80%
asymptomatic!
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Influenza
• Type A = Hong Kong, Asian, Swine flu; Avian
Influenza (bird flu – emerging disease)
• Bird  human (right now)
Pandemic: human  human; antigenic shift
Influenza pandemic of ________ killed
20+ million people! (more than plague?)
The viruses of the last three global influenza
pandemics were first found in China.
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HIV
• Retrovirus – ssRNA genome – depends on Reverse
•
•
•
•
Transcriptase to make DNA (will be covered later)
Latent phase – inserts in host genome – 2 wks. - 20
years? – can’t see virus particles in bloodstream
Infects cells – CD4+ T-cells (lymphocytes), macrophages
Destroys immune system  AIDS  person frequently
dies from 2ndary infection and/or cancer
HIV also attacks organs directly (kidney, heart)
2007 data:
• number of people living with HIV = ___________
• Number of people who died of AIDS = __________
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HIV – enveloped virus
• HIV does not survive well outside the human
body or in the outside the environment.
(Enveloped – fragile – does not survive
drying)
• The studies also shown that drying HIV reduces
the amount of viral by nearly 95 percent within
several hours.
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HIV/AIDS – stages
• Stage I: asymptomatic, not categorized as AIDS
• Stage II: include minor mucocutaneous manifestations
•
•
(ex. recurrent yeast infections) and recurrent upper
respiratory tract infections
Stage III: includes unexplained ______________
for longer than a month, severe bacterial infections
and pulmonary tuberculosis. Wasting begins.
Stage IV includes ___________of the brain,
candidiasis of the esophagus or repiratory,
Pnemocystis carinii pneumonia, and Kaposi's sarcoma
(cancer); these diseases are used as indicators of
AIDS.
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Other noncellular infectious particles
___________- misfolded proteins, contain no
nucleic acid
– Cause transmissible spongiform
encephalopathies – fatal neurodegenerative
diseases
– Common in animals:
•
•
•
•
Scrapie in sheep and goats
Bovine spongiform encephalopathies (BSE), a.k.a. mad cow
disease
Wasting disease in elk
Humans – Creutzfeldt-Jakob Syndrome (CJS)
– Extremely resistant to usual sterilization
techniques
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Figure 6.22
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Other Noncellular Infectious Agents
• Satellite viruses – dependent on other
viruses for replication
– Adeno-associated virus – replicates only in
cells infected with adenovirus
– Delta agent – naked strand of RNA
expressed only in the presence of hepatitis B
virus
• ___________ – short pieces of RNA,
no protein coat; only been identified in
plants
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