Download Viruses, viroids, and prions

10/30/2016
Viruses, viroids, and prions
Chapter 13
BIO 220
Fig. 13.1
Characteristics of viruses
• Very, very small (filterable)
• Obligatory intracellular parasite
• They have no ribosomes, so must use host cell
machinery to translate viral mRNA into viral
proteins
• Do not store or generate ATP, so energy is derived
from the host cell
• Parasitize host cell for building materials like
amino acids, lipids, and nucleotides
• Without the host cell, viruses can not carry out
“life”-sustaining processes
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Host range of virus
• Spectrum of cells virus can invade
• Most viruses can only infect specific types of
cells of only one host species
• Range determined by
– Virus must be able to interact with specific
receptor sites on host cell surface
– Availability within the specific host of cellular
factors necessary for viral multiplication
Viral structure
• Viruses are composed of a nucleic acid
surrounded by a protein coat called a capsid
• Some viruses have a lipid/protein/CHO
envelope surrounding the capsid
• A virion is a complete, fully developed,
infectious viral particle located outside a host
cell
Nucleic acids
• Virus can have DNA or RNA
• Nucleic acid can be ds or ss
• Nucleic acid may be a few thousand
nucleotides up to 250,000 nucleotides
• Nucleic acid may be circular or linear
• For some viruses, the percentage of nucleic
acid in relation to protein is about 1%
(influenza), can be up to 50% (certain
bacteriophages)
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Capsid
• This is the protein coat covering the viral
nucleic acid
• Protein subunits of capsid are called
capsomeres
• Functions:
– Protection
– Contains attachment sites
– Proteins allow viral
penetration of host cell
Fig. 13.2
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Envelopes
• Nonenveloped viruses lack an envelope
• Enveloped viruses do have an envelope
• Some viral capsids are covered by envelopes
which may be made of lipids, proteins, and
CHOs
Spikes
• May be means of attachment to host cells
• May be used as a means of identification
– May be a result of extrusion from host cell
– Viral nucleic acid codes for envelope proteins,
other components derived from the host cell
• Some envelopes may be covered in spikes
(CHO/protein complexes)
Fig. 13.3
Influenza
• HA spikes (hemagglutinin spikes)
– Binds sialic acid on host cell membranes
– Bind to erythrocytes and form cross bridges, resulting
in agglutination
– Targeted by antibodies against the influenza virus
• NA spikes (neuraminidase spikes)
– Enable virus to be released from host cell
– Required for viral replication
– Target of drugs like Tamiflu
• Spikes can be used for identification of subtypes
Influenza classification
• A – infects humans and several types of
animals (i.e. birds, horses, swine)
• B – humans
• C – humans, swine, dogs
• Influenza pandemics are caused by Type A
viruses, which are classified into subtypes
based on the HA and NA spikes
• HA (17 versions), NA (10 versions)
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Viruses are tricky
• Some viruses have evolved mechanisms for
evading antibodies (that were produced in
response to that particular virus)
– Viral genes, including those determining viral
surface proteins, are susceptible to mutation
– The progeny of mutant viruses therefore have
altered surface proteins (slight changes in spikes),
which are not recognized by the antibodies
– Antigenic drift
Viral morphology
Antigenic shift
• A major change in the virus that
results in new combinations of
HA and NA proteins
• Can take place when a human or
animal is infected with two
different subtypes of virus
• Reassortment of nucleic acids
can result in a modified virus that
humans do not have immunity to
Based on capsid architecture
•
•
•
•
Helical (rabies, Ebola)
Polyhedral (adenovirus, poliovirus)
Enveloped (influenza)
Complex
Fig. 13.4a
– Bacteriophages
Fig. 13.5a
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Classification of viruses
•
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•
•
•
Way people imagined they were contracted
Scientists that discovered them
Based on disease they produce
Animal/tissue affinity
Host range or specificity
Morphological characteristics
– Type of nucleic acid/enveloped or naked/capsid
size/capsid architecture
Plaque method
How can we grow viruses in the lab to
study them?
For animal viruses . . .
• Grow virus in live animals
• Chicken embryos
• Cell/tissue culture
Bacteriophages
• Much easier to grow in lab
Viral multiplication
• The virion nucleic acid contains only a few
genes for viral replication
– Genes for viral structural components
– Genes for enzymes used in viral life cycle (i.e.
replicating viral nucleic acid)
– Some virions contain a few preformed enzymes
– Genes are only transcribed and proteins made if
virus is in host cell
• Most everything else is supplied by host cell
Fig. 13.6
Plaque forming units – each plaque corresponds to a single virus
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Viral one-step growth curve
Bacteriophage multiplication
• The lytic cycle (T-even bacteriophage)
– Ends with the lysis and death of host cell
• The lysogenic cycle (Bacteriophage λ)
– Host cell lives
Fig. 13.10
Virulent phages
• Undergoes the lytic cycle
Phage lysozyme
• The result of the lytic cycle is viral replication
and death of the host cell as mature virions
are released
Degradation host DNA
Viral mRNA transcribed/translated
Phage components synthesized
Lysozyme
Fig. 13.11
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Induction
Temperate phages
• Can undergo a lytic or lysogenic cycle,
depending on environmental conditions
• In the lysogenic cycle the phage DNA is
incorporated into the bacterial chromosome
Prophage
gene
repression
– Prophage is inactive during this period
Fig. 13.12
• The phage DNA can be excised via induction
and then enter the lytic cycle
Some phages (temperate phages) may proceed through a lytic cycle, but also have the
ability to incorporate their DNA into the host cell’s DNA to begin a lysogenic cycle.
Consequences of lysogeny
• Lysogenic cells are immune to reinfection by the
same phage
• Phage conversion – host cell may exhibit new
properties, i.e. toxin production
– Corynebacterium diphtheriae, Clostridium botulinum
• Specialized transduction is possible
– When a prophage is excised from its host
chromosome, it can take with it a bit of the adjacent
DNA from the bacterial chromosome
Fig. 13.13
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Multiplication of animal viruses
•
•
•
•
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Attachment
Entry
Uncoating
Biosynthesis of virus
Maturation and release
The type of nucleic acid as well as whether or not the virus has an envelope
will determine the life cycle of an animal virus.
Multiplication of animal viruses
• Attachment
– Animal viruses have attachment sites that bind to
receptor sites on host cell PM
• Entry
– Many viruses enter by receptor-mediated
endocytosis
– Fusion (enveloped viruses)
Multiplication of animal viruses
• Uncoating
– This is the step where the capsid is removed from
the viral nucleic acid
• Host lysosomal enzymes
• Enzymes encoded by viral DNA that are
synthesized soon after infection
Fig. 13.14
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Biosynthesis of DNA viruses
• Generally, DNA viruses replicate their DNA in
the host cell nucleus by using viral enzymes
• Capsid synthesis in cytoplasm
• Virion assembly in nucleus
• Virions transported to PM for release
Papovavirus – naked, dsDNA
Fig. 13.15
DNA viruses
• Papovaviridae (naked)
Biosynthesis of RNA viruses
• Virus multiplies in cytoplasm
– Human papilloma virus
• Herpesviridae (enveloped)
• Adenoviridae (naked)
• Hepadnaviridae (enveloped)
• Viral RNA codes for RNA-dependent RNA
polymerase, which makes a complementary
copy of RNA
– Hepatitis B
• Poxviridae (enveloped)
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Zika virus
• ss +RNA virus, enveloped
• Member of flaviviridae
• Transmitted by Aedes mosquitos, but sexual
transmission is also possible
• Zika fever symptoms include headache, fever,
maculopapular rash, and conjunctivitis, but
symptoms vary
Synthesis of host RNA inhibited
Fig. 13.17
– Can cause a birth defect called microcephaly
– Can also cause Guillain-Barre syndrome in adults
+RNA virus (ss)
Picornaviridae (poliovirus, enterovirus)
Detection and treatment
Detection
• PCR (detection of viral RNA)
• Presence of antibodies in serum
Treatment
• None
• Vector control!
– Wolbachia
-RNA virus (ss)
Fig. 13.17
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Biosynthesis of RNA viruses that use DNA
Original viral RNA degraded
Virus may remain
in a latent state or
may be expressed
Retroviruses & oncogenic RNA viruses
Fig. 13.19
Fig. 13.17
HIV
HIV infection of target T cells
A retrovirus (Lentivirus)
Two strands of RNA
Reverse transcriptase
Phospholipid envelope
with gp120 spikes
• Spread by dendritic cells
• Activated CD4+ cells are
main target
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•
Fig. 19.13
Fig. 19.13
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Infection in CD4+ cells
Fig. 19.14
Infection in APCs
Fig. 19.15
HIV subtypes
How is HIV able to persist?
• Integrated in host genome as provirus
• Virus may not be released by infected cells
(stored as latent virions in vacuoles)
• Some infected cells become a reservoir for the
virus
• Cell-cell fusion
• Rapid antigenic changes due to reverse
transcriptase activity (high mutation rate)
• HIV-1
– Most virulent
– Accounts for 99% of cases
– Related to viruses in western Africa that affect
primates
– Further subdivided by letter . . .
• HIV-2
– Related to virus that affects the sooty mangabeys
– Not common outside of Africa
– Patients may be asymptomatic for lengthy periods
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Acquired Immunodeficiency Syndrome
(AIDS)
• Final stage of human immunodeficiency virus
(HIV) infection
• Patients susceptible to infections due to
suppressed immune activity
Fig. 19.16
HIV detection
• ELISA (detection of HIV antibodies)
• Western blots
• Real-time PCR
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HIV transmission
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Drugs that inhibit the HIV life cycle
Blood
Semen
Intimate sexual contact
Breast milk
Transplacental
Blood-contaminated needles
Organ transplants
Artificial insemination
Blood transfusion
Fig. 19.18
Maturation and release
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•
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Budding
Capsid is assembled
Nucleocapsid forms
Naked viruses cause rupture of the host cell
Enveloped viruses often leave the host cell via
a process called budding
– Envelope proteins are encoded by viral genes and
are inserted in host cell PM
– Envelope forms as virion leaves the host
Fig. 13.20
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Transformation of normal cells into cancer
cells
• Can be due to viruses
• Cancer-inducing genes (oncogenes) carried by viruses
are actually derived from animal cells
• Oncogenes can be activated to abnormal functioning
by a variety of factors
• Oncogenic viruses can induce tumor formation
– Virus integrates into host cell DNA and replicates along
with the host cell DNA, ultimately transforming host cell
• After being transformed by viruses, tumor cells contain
a virus-specific antigen on their cell surface (tumorspecific transplantation antigen (TSTA) or in the nucleus
(T antigen)
DNA oncogenic viruses
• Adenoviridae
• Herpesviridae
– Epstein-Barr virus
• Poxviridae
• Papovaviridae
– Human papillomaviruses
• Hepadnaviridae
– Hepatitis B
RNA oncogenic viruses
• Retroviridae
– Leukemia virus
Viruses to treat cancer
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Adenovirus (H101)
Talimogene laherparepvec (T-VEC)
Reolysin
Delta 24 cold virus
Modified measles
Modified herpesvirus
Modified HIV
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Viral infections
Latent and persistent viral infections
• A latent viral infection is one in which the virus
remains quiet or latent within a host cell and
does not produce disease for an extended
period, perhaps years
• Persistent viral infections occur gradually over
an extended period of time
Fig. 13.21
Prions
• Proteinaceous infectious particle
• Cause diseases such as kuru, Creutzfeldt-Jakob
disease, fatal familial insomnia, mad cow
disease, scrapie which are characterized by
spongiform encephalopathies
• Disease is caused by the conversion of a
normal host glycoprotein (PrPC) into an
infectious form (PrPSc)
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Plant viruses and viroids
• Plant viruses are morphologically similar to
animal viruses and have similar types of
nucleic acids
• Because of the presence of the plant cell
walls, viruses typically gain access through
wounds or are assisted by other parasites
(nematodes, fungi, insects)
• Some plant diseases are caused by viroids,
which consist of naked RNA
Fig. 13.22
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