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Viruses, viroids, and prions
Chapter 13
BIO 220
Fig. 13.1
Characteristics of viruses
• Very, very small (filterable)
• Obligatory intracellular parasite
• Viruses are composed of a nucleic acid, a
protein coat , sometimes an envelope
• Viruses produce few (if any) enzymes
• 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 host 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 (i.e. cell wall, plasma membrane, part of fimbriae or flagella)
– Availability within the specific host of cellular factors necessary for viral multiplication
Why do we care about viruses?
• They causes illness and disease
• Maybe we can use them to treat disease
– Phage therapy
• An alternative to antibiotics?
– Oncolytic viruses
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
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/or CHOs
– 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)
Spikes
• May be means of attachment to host cells
• May be used as a means of identification
Fig. 13.3
Influenza
• HA spikes (hemagglutinin spikes)
– Binds sialic acid on host cell membranes
– Mediates fusion between virus and host cell membrane
– Main antigenic sites on virus
• NA spikes (neuraminidase spikes)
– Enable virus to be released from host cell
– Target of drugs like Tamiflu and Relenza
• Spikes can be used for identification of subtypes of the virus
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Influenza classification
• A – infects humans and several types of
animals (i.e. birds, horses, swine)
• B – humans
• C – humans, less frequently swine and dogs
• D – cattle
• 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)
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 – a gradual, continuous change
Antigenic shift
• A major change in the virus that
results in new combinations of
HA spikes or 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
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Viral morphology
Based on capsid architecture
• Helical (rabies, Ebola)
• Polyhedral (adenovirus, poliovirus)
• Enveloped (influenza)
• Complex
– Bacteriophages
Fig. 13.5a
Fig. 13.4a
Classification of viruses
• Way people imagined they were contracted or symptomology
• 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
Viral species
• A group of viruses sharing the same genetic
information and ecological niche (host range)
• No specific epithets
• Designated by descriptive common names,
with subspecies designated by a number
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
Figs. 13.7 & 13.8
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Plaque method (Bacteriophages)
Fig. 13.6
Theoretically, each plaque corresponds to a single virus in the initial suspension.
Viral multiplication
• The virion nucleic acid contains only a few genes for the synthesis of new virus
– Genes for viral structural components
– Genes for some of the 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
Viral one-step growth curve
Fig. 13.10
Bacteriophage multiplication
• The lytic cycle
• The lysogenic cycle
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Virulent phages
• Undergoes the lytic cycle
• The result of the lytic cycle is viral replication
and death of the host cell as mature virions
are released
• T-even bacteriophages
Phage lysozyme
Degradation host DNA
Viral mRNA transcribed/translated
Phage components synthesized
Lysozyme
Fig. 13.11
Temperate phages aka lysogenic 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” is inactive during this period
• The phage DNA can be excised via induction and then enter the lytic cycle
Fig. 13.12
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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
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.
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Multiplication of animal viruses
• Attachment
• Entry
• Uncoating
• Biosynthesis of virus
• Maturation and release
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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)
Fig. 13.14
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
– Location of uncoating depends on virus
Biosynthesis of DNA viruses
• Generally, DNA viruses replicate their DNA in the host cell nucleus by using viral enzymes
• Capsid synthesis in cytoplasm by using host cell enzymes
• Virion assembly in nucleus
• Virions transported to PM for release via ER
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Fig. 13.15
Papovavirus – naked, dsDNA
Viral DNA enter nucleus,
Transcription of early genes
carried out by host RNA pol
After replication of viral DNA has
begun, transcription/translation
of “late” genes occurs
Biosynthesis of RNA viruses
• Virus multiplies in cytoplasm
• Viral RNA codes for RNA-dependent RNA
polymerase, which makes a complementary
copy of RNA
Fig. 13.17
+RNA virus (ss), naked
Picornaviridae (poliovirus, enterovirus)
Viral RNA translated, resulting
proteins (1) (-) synthesis of
host RNA, (2) RNA-dependent
RNA polymerase
Antisense strands serve as template for
making more sense RNA, Sense strand
serves as RNA template, translated,
inserted in capsid
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
– Can cause a birth defect called microcephaly
– Can also cause Guillain-Barre syndrome in adults
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Detection and treatment
Detection
• PCR (detection of viral RNA)
• Presence of antibodies in serum
Treatment
• None
• Vector control!
– Wolbachia
Fig. 13.17-RNA virus (ss), enveloped
Antisense RNA can’t be used as
mRNA, so RNA-dependent RNA
polymerase a part of the virion
Sense RNA a template for more antisense
RNA production & also translated, Antisense
RNA packaged into capsids, template for
sense RNA
Biosynthesis of RNA viruses that use DNA
Fig. 13.19
Retroviruses & oncogenic RNA viruses
Original viral RNA degraded
Virus may remain
in a latent state or
may be expressed,
but is not removed
from chromosome
Capsids contain
reverse transcriptase,
integrase, protease
HIV
• A retrovirus (Lentivirus)
• Two strands of +RNA
• Reverse transcriptase
• Phospholipid envelope
with gp120 spikes
• Spread by dendritic cells
• Activated CD4+ cells are
main target
Fig. 19.13
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HIV infection of target T cells
Fig. 19.13
Infection in CD4+ cells
Fig. 19.14
Infection in APCs
Fig. 19.15
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)
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HIV subtypes
• 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
Fig. 19.16
Acquired Immunodeficiency Syndrome
(AIDS)
• Final stage of human immunodeficiency virus
(HIV) infection
• Patients susceptible to infections due to
suppressed immune activity
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HIV detection
• ELISA (detection of HIV antibodies)
• Western blots
• Real-time PCR
HIV transmission
• Blood
• Semen
• Intimate sexual contact
• Breast milk
• Transplacental
• Blood-contaminated needles
• Organ transplants
• Artificial insemination
• Blood transfusion
Drugs that inhibit the HIV life cycle
Fig. 19.18
Multiplication of animal viruses
• Attachment
• Entry
• Uncoating
• Biosynthesis of virus
• Maturation and release
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Maturation and release
• 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
Budding
Fig. 13.20
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 (tumor-specific transplantation antigen (TSTA) or in the nucleus (T antigen)
DNA oncogenic viruses
• Adenoviridae
• Herpesviridae
– Epstein-Barr virus
• Poxviridae
• Papovaviridae
– Human papillomaviruses
• Hepadnaviridae
– Hepatitis B
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RNA oncogenic viruses
• Retroviridae
– T-cell leukemia virus
– Feline leukemia virus
Viruses to treat cancer
• Adenovirus (H101) – head/neck/lung cancer
• Talimogene laherparepvec (T-VEC) - melanoma
• Reolysin
• Delta 24 cold virus – brain cancer
• Modified measles – myeloma
• Modified herpesvirus
• Modified HIV - leukemia
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
– i.e. Varicella-zoster virus
• Persistent viral infections occur gradually over
an extended period of time
– Usually fatal
Latent and persistent viral infections
Fig. 13.21
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Prions
• Proteinaceous infectious particle
• Cause diseases such as kuru, Creutzfeldt-Jakob
disease, fatal familial insomnia, mad cow
disease, and scrapie which are neurological
diseases called spongiform encephalopathies
• Disease is caused by the conversion of a
normal host glycoprotein (PrPC) into an
infectious form (PrPSc)
Fig. 13.22
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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