Chapter 12 Outline
The Viruses and Virus-Like Agents
Introduction
12.1 Foundations of Virology
• Many Scientists Contributed to the Early Understanding of Viruses
• Dimitri Ivanowsky and Martinus Beiherinck studied the tobacco mosaic
virus
• Walter Reed studied foot-and-mouth disease and yellow fever
• Frederick Twort and Felix d’Herelle studied bacteriophages
• In the 1930s, it was discovered that viruses are nonliving agents composed
of nucleic acid and protein
• Alice M. Woodruff and Ernest W. Goodpasture developed a culture
technique using chicken eggs
12.2 What are Viruses?
• Viruses Are Tiny Infectious Agents
• Viruses are small, obligate intracellular parasites
• They lack the machinery for generating energy and large molecules
• They need a host eukaryote or prokaryote to replicate
• The viral genome contains either DNA or RNA, but not both
• The capsid is the protein coat, made up of capsomeres
• The nucleocapsid is the capsid with its enclosed genome
• Some capsid proteins are spikes that help the virus attach to and penetrate
the host cell
• Naked viruses are composed only of a nucleocapsid
• Viruses surrounded by an envelope are enveloped viruses
• A virion is a completely assembled, infectious virus outside its host cell
• Viruses Are Grouped by Their Shape
• Helical viruses have helical symmetry
• Isocahedral viruses have isocahedral symmetry
• Viruses that have both helical and isocahedral symmetry have
complex symmetry
• Viruses Have a Host Range and Tissue Specificity
• A host range refers to what organisms the virus can infect
• Host range depends on capsid structure
• Many viruses infect certain cell or tissue types within the host (tissue
tropism)
12.3 The Classification of Viruses
• Nomenclature and Classification Do Not Use Conventional Taxonomic Groups
• Viruses can be named according to a number of different conventions
• The International Committee on Taxonomy of Viruses (ICTV) is
developing a classification system
• DNA viruses contain single- or double-stranded DNA genomes
• RNA viruses contain single- or double-stranded RNA genomes
• + strand RNA viruses have mRNA genomes
•
– strand RNA viruses have RNA strands that would be complementary to
mRNA
• Retroviruses are replicated indirectly through a DNA intermediate
12.4 Viral Replication and its Control
• The Replication of Bacteriophages Is a Five-Step Process
• T-even group bacteriophages are virulent viruses that carry out a lytic
cycle of infection
• The phage nucleic acid contains only a few of the genes needed for viral
synthesis and replication
• Phase 1: Attachment occurs when a phage’s tail fibers match with a
receptor site on the bacterium’s cell wall
• Phase 2: Penetration occurs when the phage tail releases lysozyme to
dissolve a portion of the cell wall
• Phage DNA is injected into the bacterial cytoplasm
• Phase 3: Biosynthesis is the production of new phage genomes and capsid
parts
• Phase 4: Maturation is the assembly of viral parts into complete virus
particles
• Phase 5: Release is the exit of virions from the bacterium
• It is also called the lysis stage when the cell is ruptured
• Temperate phages do not lyse the host
• They insert their DNA into the bacterial chromosome as a prophage
(lysogenic cycle)
• Animal Virus Replication Has Similarities to Phage Replication
• Animal viruses attach to host plasma membrane via spikes on the capsid
or envelope
• Since receptor sites vary from person to person, some people are more
susceptible to a certain virus than others
• Animal viruses are usually taken into the cytoplasm as intact
nucleocapsids
• Uncoating is the separation of the capsid from the genome
• This occurs as some animal viruses enter the cell
• After the new viruses are assembled, envelope proteins are incorporated into a
cellular membrane
• The virus buds, taking the membrane part with it as an envelope
• Some Animal Viruses Can Exist as Proviruses
• Some DNA viruses and retroviruses insert their genome into the host
chromosome as a provirus
• Retroviruses use reverse transcriptase to transcribe their RNA to DNA
• It can then be inserted into the host chromosome
• The provirus encodes a repressor protein that prevents activation of the
viral genes necessary for replication
• It is in a state of latency
• Latent proviruses are immune to the host body’s defenses
•
They are propagated each time the cell’s chromosome is
reproduced
• Eventually the provirus will be activated and replicate
• Antiviral Drugs Can Be Used to Treat a Limited Number of Human Viral
Diseases
• Antibiotics do not work against viruses
• Viruses lack the elements with which antibiotics interfere
• Some antivirals exist to affect:
• viral penetration/uncoating
• genome replication
• maturation/release
• Most antivirals target the replication enzymes of the virus by
• inserting base analogs in the replicating DNA strand
• blocking replication of the viral genome
• Reverse transcriptase inhibitors prevent the synthesis of DNA in
retroviruses
• Protease inhibitors impede the HIV protease that trims viral proteins in
capsid construction
• Neuraminidase inhibitors block an enzyme in the spike of influenzaviruses
• This prevents the release of new virions into the body
• Interferon Puts Cells in an Antiviral State
• Interferon (IFN) is a group of naturally-produced proteins that alert cells
to a viral infection
• Some IFNs have anti-cancer properties
• Cells in an antiviral state can inhibit viral replication by preventing protein
synthesis
• IFNs bind to receptors on cells, triggering them to produce antiviral
proteins
12.5 The Cultivation and Detection of Viruses
• Detection of Viruses Is Often Critical to Disease Identification
• Rivers’ postulates expand upon Koch’s postulates to help identify viruses
• Filtrates of infectious material shown not to contain bacterial or
other cultivatable organisms must produce the disease or its
counterpart
• Filtrates must produce specific antibodies in appropriate animals
• Cytology uses light microscopy to examine cells for cytopathic effects
(CPEs) of viral infection
• Occasionally, viruses can be observed directly by electron microscopy
• Cultivation and Detection of Viruses Most Often Uses Cells in Culture
• In a primary cell culture, cells form a monolayer in a culture dish
• The type of cell culture depends on the virus to be cultivated in the
monolayer
• Viruses can be detected by the formation of plaques, a clear zone within
the monolayer
12.6 Cancer and Viruses
• Cancer Is an Uncontrolled Growth and Spread of Cells
•
•
•
A tumor is a clone of abnormal cells
Normally, the body surrounds a tumor with a capsule of connective tissue
• a benign tumor
Tumor cells can break free from the capsule and spread to other tissues of
the body (metastasis)
• a malignant tumor
• Viruses Are Responsible for Up to 20% of Human Tumors
• 60–90% of human cancers are associated with carcinogens
• Oncogenic viruses include:
• Epstein-Barr virus is linked to Burkitt Lymphoma, a tumor of the
jaw
• Human papilloma virus (HPV) is associated with cervical cancer
– There is now a vaccine against the 2 most common strains
of HPV
• Oncogenic Viruses Transform Infected Cells
• The oncogene theory suggests that protooncogenes normally reside in the
chromosomal DNA of a cell
• They can be transformed to oncogenes by:
• radiation
• chemical carcinogens
• DNA damage
• viruses
• Sometimes a virus inserts its DNA (as a provirus) into a cell’s
chromosome next to a protooncogene
• When virus replication is triggered, the provirus replicates its only
DNA as well as a few adjacent host genes
• V-oncogenes are protooncogenes captured in the viral genome
• When the oncogenic viruses infect another cell, the v-oncogene is
under the virus’ control, not the cell’s control
• The v-oncogene can then code for growth factors, stimulating
uncontrolled cell proliferation
12.7 Emerging Viruses and Viral Evolution
• Emerging Viruses Usually Arise Through Natural Phenomena
• Emerging viruses may spread to new populations, or may expand host
range
• Genetic recombination can lead to “new” viruses
• Mutation can occasionally be advantageous and create a new virus or stain
of virus.
• There Are Three Hypotheses for the Origin of Viruses
• The regressive evolution hypothesis:
• Viruses are degenerate life-forms
• The cellular origins hypothesis:
• Viruses are derived from subcellular components and
macromolecules that escaped from cell walls and replicated inside
hosts
•
The independent entities hypothesis:
• Viruses coevolved with cellular organisms from a self-replicating
molecule present on primitive Earth
12.8 Virus-Like Agents
• Viroids Are Infectious RNA particles
• Viroids are tiny fragments of RNA that cause diseases in crop plants
• The replication cycle and disease causation process of viroids are not
understood
• One hypothesis suggests they originated as introns
• Prions Are Infectious Proteins
• Transmissible spongiform ecephalopathies (TSEs) can occur in humans
and other animals
• For example, mad cow disease
• TSEs are neurologic degenerative diseases that can be transmitted within
or between species
• Originally, scientists believed TSEs were caused by a virus
• Stanley Prusiner discovered the proteinaceous infectious particle (prion)
• The protein-only hypothesis predicts that prions are composed only of
protein and contain no nucleic acids
• Normal cellular prions have a different shape than abnormal prions, the
latter of which cause TSEs
• TSEs may spread when infectious prions bind to normal prions
• This causes normal prions to change shape and become abnormal
• Abnormal prions do not trigger an immune response
• Death of the host occurs from nerve cell death leading to sponge-like holes
in brain tissue
• Symptoms include:
– dementia
– weakened muscles
– loss of balance
• This results from insoluble aggregates of abnormal prions in the
brain
• The human form of TSE is called variant CJD (Creutzfeldt-Jakob disease)