VIRUSES
A. What
are viruses?
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Virion: a complete virus particle that consist of
DNA or RNA molecule enclosed in a coat of protein.
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Viruses can exist in two phases:
o
Extra
Cellular
Virions:
posses few enzymes if any and cannot reproduce
independently of living cells.
o
Intra
Cellular
Viruses exist primarily as replicating
nucleic acids that induce host metabolism to synthesize
virions, complete virus particles.
1. Problems
a. Viruses are too small to be seen under the
light microscope (~65 nm).
b. Viruses can’t be grown in the absence of
the host cell: obligate intracellular parasites.
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Animal, plant, insect, and bacterial (bacteriophage)
viruses
2. Solutions
a. development of the electron microscope
b. development of cell culture techniques
to grow viruses
c. Bacteriophage
assay
(1) Mix virus and bacterial cells in a test
tube that contains 0.7% agar (“soft agar”).
(2) Pour contents of tube onto the surface of a
nutrient agar plate and let solidify.
(3) Incubate for 24 hours.
(4) Result in Plaques:
a “lawn” of bacteria pockmarked by
clear spots of viral growth.
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Each plaque is assumed to arise from a single
infectious virus particle.
3. Tissue culture techniques for animal viruses
were developed in the 1950’s.
Virus morphology
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10-300 nm in
size (recall that limit of resolution of the best light microscopes is about
200 nm).
Shape
(1) filamentous (tubular); e.g., tobacco
mosaic virus
(2) polyhedral (roughly spherical);
e.g., adenovirus (causes respiratory infections, different than rhinovirus
which causes colds)
(3) combined (polyhedral head
attached to a filamentous tail); e.g., E. coli bacteriophage T4
Enveloped viruses are surrounded by a lipid
membrane.
Envelope is
common in animal viruses that “bud” out of the
host cell.
Chemical composition
§
All virions are constructed around a nucleocapsid core which is composed of
a
o
Nucleic acid (DNA or RNA) held within a protein coat
called the capsid.
o
Capsid:
-- Head consists of a hollow protein shell that encloses the viral nucleic acid.
-- Protects the viral genetic
material and aids in the transfer between host cells.
(1) All cells
contain dsDNA as their genetic material.
(2) In different viruses, the genetic material
may be dsDNA, ssDNA, dsRNA, or ssRNA.
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Tail (if present)
is composed of protein.
Outside of the host cell, the virus particle (virion)
is completely
inert: no
metabolism or other biological activities.
How do viruses grow?
Growth of bacteriophages:
a. Lytic
growth (ex: bacteriophage T4, animal and plant viruses infect through a
similar set of steps)
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Lytic Cycle: Life cycle that culminates with the host
cell bursting and releasing virions.
(1) Adsorption: binding to a specific component of the host
cell surface (receptor).
(2) Penetration: injection of viral nucleic acid into the
host cell cytoplasm by passage through the hollow tail tube (due to syringe
action of the contractile sheath).
(3) Reproduction
of viral components: protein synthesis
and nucleic acid replication using mostly host cell machinery.
(4) Assembly
of viral components into intact viral particles.
(5) Release
through lysis of the host cell (an alternative used by some viruses is
extrusion through the host cell membrane, doesn't necessarily kill the cell).
(6) During lytic growth, a single bacteriophage
particle infecting a bacterial cell can typically produce 50-200 progeny in 30-40 minutes.
b. Lysogenic
growth (ex: E. coli bacteriophage l)
(1) adsorption
(2) penetration
(3) Integration of the viral DNA into
the bacterial chromosome, where it is carried as a “silent” genetic element (prophage).
(4) However, the potential for lytic growth
remains.
(5) Environmental stress (UV light, exposure to
DNA-damaging chemicals, etc.) triggers excision of the viral DNA from
the bacterial chromosome and the resumption of lytic growth.
(6) Only some, not all, phages are capable of
lysogenic growth.
c. Lytic growth can be thought of as a “hit and
run” strategy for viral reproduction and lysogenic growth as a “playing the
waiting game” strategy.
Growth of animal viruses
a. Virus multiplication is similar to
bacteriophage lytic growth (uncoating during phagacytosis versus injection,
some lytic and others bud out from the cell (enveloped) => persistent
infection (may not kill cell, but cell not function normally, other effects
like surface enzymes that lyse red blood cells and immune system reacts to
cell).
b. latent infection - delay
between first infection and appearance of symptoms.
3. Retroviruses
(ex: HIV causative agent of AIDS )
a. Growth of retroviruses
(1) Virus particles contain ssRNA.
(2) In the host cell, the viral enzyme reverse
transcriptase synthesizes dsDNA using viral RNA as the template.
(3) Viral DNA then integrates into host cell
chromosomes where it directs viral reproduction.
(- can be a
latent infection, can remain dormant, incorporated in genome of host)
b. Some retrovirus infections can transform
the host cell (from normal into malignant).
(1) The genetic material of some retroviruses
contains an oncogene (cancer-causing gene or tumor suppressor gene)
which is responsible for the transformation.
(2) About 20 different oncogenes have been
identified so far.
c. Potential oncogenes (proto-oncogenes)
have been found in normal, uninfected cells.
Proto-oncogenes encode proteins that stimulate the proliferation of
cells.
d. Retroviral oncogenes are slightly altered
versions of cellular proto-oncogenes.
e. Hypothesis: retrovirus incorporates cellular proto-oncogenes from the host
cell DNA in a mutated form (activated to function as oncogenes).
f. Every cell in the body contains
proto-oncogenes that could turn the cell malignant under the appropriate
conditions. What factors influence this
process?
(1) environmental effects
(2) genetic effects
g. It is estimated that up to 20% of all human
cancers are caused (at least in part) by chronic viral infections.
h. Viruses that are implicated in human
cancers (weaken immune system (ex-AIDS) or deliver oncogenes):
(1) Retroviruses:
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Human T-cell Leukemia virus (HTLV-1) and
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Human Immunodeficiency Virus (HIV)=Kaposi's lymphoma
(cancer of the lining of the blood vessels).
(2) DNA
viruses:
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Human
Papilloma Virus
cervical cancer, may be due to coinfection with
cancer causing herpes virus
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Epstein-Barr Virus
Nasopharyngeal cancer and
Burkitt’s lymphoma: a cancer of the lymph
glands
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Hepatitis B Virus - liver cancer
Other viral diseases of animals: herpes,
smallpox, rabies