Download C. Primary Morphological types[3]

VIRUSES
Why don’t antibiotics work against viruses?
12/01/09
I. Introduction
II. On the edge of life…
III. General Characteristics
IV. DNA Review
V. Lytic and Lysogenic Life Cycles
VI. Example of the Infection Process: HIV Retrovirus
VII. Cancer
VIII. Bacteriophages Which Carry Genes For Human Toxins
IX. Viroids, Virusoids, and Prions
I. Introduction
A. Tobacco mosaic virus: First virus to be recognized as an infectious agent dependent on a host
cell to replicate. (late 1800s). TMV was not actually ‘seen’ until the advent of the electron
microscope (1930’s?)
B. Difficulties in isolating and studying viruses:
1. Size: VERY small, along the nanometer range (10-9m)
2. Obligate intracellular reproduction: Can only reproduce inside of a living cell
3. Host and Tissue Specific: Will only infect a limited number of host species and tissues
within those hosts
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Most forms of life are composed of cells. A cell is considered to be the basic unit of life -consisting of a
membrane-enclosed cytoplasm with various structures and substances which carry out life’s functions.
Viruses are not composed of ‘cells’ but do have some similarities. Viruses are not composed of cells,
but they require a cell to replicate (reproduce).
II. On the edge of life…
‘Cellular’ Characteristics of Viruses
Viruses do contain surface molecules that
allow the virus to bond to its specific host
cells. This bonding initiates the infection
process and allows the virus to enter the host
cell.
1. Viruses contain genetic material.
However, all cells use double-stranded DNA
as the genetic (hereditary) material. Cells
also contain DNA and RNA simultaneously.
‘Acellular’ (noncellular)
Characteristics of Viruses
Viruses are NOT composed of cells. They
are metabolically inert until they infect their
host cell. They have no ribosomes, no way of
acquiring energy and nutrients, and lack
many structures and molecules that carry out
the functions of life.
1. Depending on the type of virus, the genetic
(hereditary) material is one of the following:
-Single-stranded DNA (ssDNA)
-Double-stranded DNA (dsDNA)
-Single-stranded RNA (ssRNA)
-Double-stranded RNA (dsRNA)
2. Viruses do not contain RNA and DNA
simultaneously in the infecting virion1.
2. Viruses reproduce
2. However, viruses must utilize the host
cell’s structures and materials (e.g.,
ribosomes, amino acids, nucleotides,
enzymes, energy) in order to undergo protein
synthesis, genome replication, and
reproduction.
3. Viruses mutate and evolve- i.e., genetically
change over time
1 The VIRION is the complete infective virus particle
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III. General Characteristics
A. Size: approximately ~20-300 nm2
The head of a dress-maker's pin can provide seating accommodation for five hundred million rhinoviruses (one cause
of the common cold)! http://web.uct.ac.za/depts/mmi/stannard/linda.html
B. Basic components of a viral particle
http://web.uct.ac.za/depts/mmi/stannard/linda.html
Terminology
1. Nucleic Acid: RNA (ds or ss) or DNA (ds or ss).
2. The CAPSID denotes the protein shell that encloses the nucleic acid. It is built of repeating
structure units.
“In 1956, Crick and Watson … pointed out that the nucleic acid in small virions was probably
insufficient to code for more than a few sorts of protein molecules of limited size. The only
reasonable way to build a protein shell, therefore, was to use the same type of molecule over and
over again, hence their theory of identical subunits, symmetrically packed to form the protein
shell.”
3. CAPSOMERS are repeating units seen on the surface of viral particles.
4. The capsid together with its enclosed nucleic acid is called the NUCLEOCAPSID.
5. Enzymes: Some viruses have one or a few enzymes inside the capsid.
6. The nucleocapsid may be contained in an ENVELOPE which contains material from the last
host cell as well as from viral origin. It is derived from the cell membrane of the viruses last
host cell.
2 Nanometer (one billionth of a meter)
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C. Primary Morphological types3
http://web.uct.ac.za/depts/mmi/stannard/linda.html
Lots of viral pictures: http://www.virology.net/Big_Virology/BVunassignplant.html
1. Helical viruses:
Capsomeres are arranged around the spiral genetic material.
Example: Tobacco Mosaic Virus (TMV) shown here in cartoon form (capsid cut away to show nucleic
acid) and an electromicrograph.
TEXT Fig. 13.4 a and b
3 Other structures are possible. These are the primary morphological types.
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2. Polyhedral viruses
(Example: Icosahedron- 20 equal-sized triangular faces).
3. Enveloped viruses: Are surrounded by an envelope derived from the host cell through
budding. TEXT Fig. 13.20 Budding
a.
Colored scanning electron micrograph of a single HIV budding from a T4
cell.
b. Herpesviruses have an envelope surrounding an icosahedral capsid, approximately
100nm in diameter, which contains the dsDNA genome. When the envelope breaks
and collapses away from the capsid, negatively stained virions have a typical "fried-egg"
appearance.
TEXT Fig. 13.16 b
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c. TEXT Fig. 13.3 Morphology of an enveloped helical virus
d. HPV (polyhedral enveloped- see spikes in envelope)
Notice ‘spikes’ on the surface.
Used for attachment to host cells.
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4. Complex viruses TEXT Fig. 13.5
a. Bacteriophage T4
b. Text
Fig. 13.5
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V. Lytic and Lysogenic Life Cycles
A. Lytic Life Cycle
1. The lytic life cycle results in the immediate production of new virions.
2. After attaching and entering the host cell, the virus shuts down the host cell’s ability to
replicate its own (host’s) DNA and/or to produce its own (host’s) enzymes.
3. Instead, the virus directs the cell to synthesize viral proteins and replicate viral genetic
material.
4. Many virions are produced (assembled) and rupture (lyse) or ‘bud out’ of the cell.
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B. Lysogenic Life Cycle
1. Viruses capable of a lysogenic life cycle can either replicate by means of the lytic life
cycle and cause immediate lysis of the host cell, or, it can become ‘latent’ (dormant) in
the cell for an indefinite period of time.
2. Two Forms
Form 1: Some lysogenic viruses insert their DNA into the host chromosome
indefinitely.
a. The viral DNA, while in the host chromosome, is called a PROVIRUS or
PROPHAGE (bacterial provirus).
b. The viral DNA is replicated whenever the host chromosome is replicated, for
example, before the cell, itself, divides. Each of the daughter cells, therefore, will
have a copy of the viral DNA (i.e., the virus is replicated, also.
Form 2: Some lysogenic viruses form a circular PLASMID with their DNA in the
cytoplasm of the host cell for an indefinite period of time.
a. After the viral DNA has circularized into a plasmid, the plasmid also is called a
provirus or a prophage (bacterial).
b. The plamid will replicate when the host cell chromosome(s) replicates before
cell division and both daughter cells will contain the plasmid (virus also,
therefore, replicated).
c. At some point, these proviruses may begin protein synthesis and replication of
the viral genetic material. Then, new virions will be produced which either bud
out of the host cell or kill/rupture the host cell.
Lysogenic virus ‘triggers’: Cell stress
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VI. Example of the Infection Process: HIV retrovirus
A.
Retroviruses: ssRNA viruses that use the enzyme reverse transcriptase during
their life cycle.
Reverse transcriptase synthesizes double-stranded DNA molecule from the
viral RNA.
ssRNA
ssDNA/ssRNA
dsDNA
B. Retroviruses have been known to cause cancer.
For example, Kaposi’s Sarcoma
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C. Multiplication of a retrovirus
1) Virus attaches to receptor sites on the surface of the host cell. HIV has proteins on its
envelope (gp120) that are strongly attracted to the CD4 surface receptor on the outside of the T4cell4. When HIV binds to a CD4 surface receptor, it activates other proteins on the cell's surface,
allowing the HIV envelope to fuse to the outside of the cell.
2) After the binding process, the viral capsid (contains the RNA and important enzymes) is
released into the host cell. ‘Uncoating’ releases the viral genetic material and enzymes.
4 At least one other cell surface receptor, the 7-transmembrane receptor, is necessary for HIV attachment. gp41 is an envelope
protein partly embedded in the virus membrane, which enables it to bind with gp120 on the far side of the membrane. When a
HIV particle binds to a cell, the interaction of gp120 with CD4 changes gp120's shape. This in turn changes the shape of gp41, in
such a way that the gp41 helps to initiate the process of membrane fusion between virus and cell.
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3) The viral enzyme reverse transcriptase makes a dsDNA copy of the RNA. This new dsDNA is
calleda “provirus”. After the dsDNA is made, the reverse transcriptase then degrades the
original viral ssRNA.
4) The HIV DNA is then carried to the cell's nucleus, where the cell's DNA is kept. Then,
another viral enzyme called integrase incorporates the proviral DNA into the cell's DNA.
Two things can occur at this point...
a. The host may divide, and in so doing replicate the proviral DNA along with the host
DNA.
OR
b. The provirus may direct the cell to produce new HIV (Go to 5).
5) HIV RNA is synthesized by the cell.
6) HIV proteins are synthesized by the cell.
Long strings of proteins are ‘cut up’ into smaller functional proteins by a viral enzyme, called
protease. These proteins serve a variety of functions; some become structural elements of new
HIV, while others become enzymes, such as reverse transcriptase.
7) Once the new viral particles are assembled, they bud off the host cell, and create new virions.
These viruses are then able to infect new cells.
As it buds out of the host cell, the virus acquires an envelope.
The following site is an excellent overview and animation of the HIV infection process and a
discussion of anti-HIV treatments.
http://www.youtube.com/watch?v=RO8MP3wMvqg
HIV websites: http://www.cdc.gov/hiv/dhap.htm
Overview of cell infection:
http://www.cellsalive.com/hiv0.htm
http://www.cdc.gov/hiv/bscience.htm
Transmission/symptoms/stages:
http://www.hivaidssearch.com/FACTS/
Testing procedures:
http://www.thestophivsite.com/HIV_tests.jsp
Statistics:
http://www.poz.ca/aids_clock.htm
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VII. Cancer
Cancer is often a result of the incorporation of retrovirus or dsDNA viral genetic material into
the host cell chromosomes. There are three major processes by which these viruses cause
cancer.
A. Viral Oncogenes: These genes enter the host cell with the other viral genetic
material. During the infection process, the viral oncogenes are incorporated into the host
cell chromosome (along with the other viral DNA).
Viral oncogenes are defective forms of human genes that normally would control host
cell division. These genes were ‘picked up’ by a virus during a previous infection. Since
they are defective, they cannot regulate host cell division correctly.
B. Host cell (‘cellular’) oncogenes: Defective forms of genes that usually control host
cell division. These oncogenes are found in the host cell chromosomes before viral
infection but usually are not ‘turned on’. They are turned on after viral infection.
C. Host cell proto-oncogene: Healthy host cell genes that normally function to regulate
cell division. The protein product is healthy UNLESS... the virus mutates the gene after
viral infection.
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VIII. Bacteriophage that carry genes for human toxins
A. Some bacteria only cause human disease or become more virulent when they,
themselves, have been infected with a prophage.
1. Phage DNA may carry toxin genes which allow the bacteria to harm human
hosts (that the bacteria have infected).
2. Without the phage DNA incorporated into the bacterial chromosome or
forming a plasmid in the bacterial cytoplasm and providing toxin genes to the
bacterium, the bacteria may not be harmful or as harmful to the human host.
B. Examples:
1. Corynebacterium diphtheriae: bacterium only capable of causing diphtheria if
it carries a specific phage with a certain toxin gene.
a. Diphtheria: upper respiratory infection which can block the passage of
air to the lungs and cause heart/kidney failure
b. Bacteriophage toxin: highly virulent, only 0.01mg can kill a 200 lb.
person; it interferes with host cell protein synthesis
2. Streptococcus pyogenes: bacterium only capable of causing scarlet fever if it
carries a specific phage that produces the erythrogenic (reddening) toxin.
-The toxin produces a pinkish-red skin rash (due to an allergic reaction to the
circulating toxin) and a high fever.
3. Clostridium botulinium: the phage gene responsible is a NEUROTOXIN
causing progressive paralysis (death due to paralysis of heart and respiratory
muscles).
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IX. Viroids, Virusoids, and Prions
A. Viroids and Virusoids are the smallest and simplest form of all recognized selfreplicating molecules.
1. Viroids are composed of nothing more than a single strand of RNA, and lack
even a protective shell of protein. Replicating in the nuclei of plant cells, they
often cause striking diseases in their host plants, such as potato spindle-tuber
disease, cucumber pale fruit, citrus exocortis disease, and cadang-cadang
(coconuts).
2. Virusoids are also small ssRNA molecules. Virusoids "infect" other RNA
viruses.
http://www.bookrags.com/research/viroids-and-virusoids-gen-04/
B. Prions (proteinaceous infectious particle)
1. Responsible for a group of transmissible and/or inherited
neurodegenerative diseases including Creutzfeldt-Jakob disease, kuru, and
Gerstmann-Straussler syndrome in humans, as well as scrapie in sheep and
goats.
2. Most evidence indicates that the infectious prion proteins are modified forms of
normal proteins found in all animals and is coded for by a gene on chromosome 20 in
humans.
3. Altered abnormal proteins interact with the normal proteins and this interaction
causes a change in the folding pattern of the normal protein. The normal protein is
now abnormally folded. The new abnormally shaped protein can then interact with
other, normal protein molecules, converting them also. Consequently, over time there
is an exponential increase in the number of dysfunctional proteins within the cell.
Why this alteration of a normal protein to an abnormal shape results in brain damage is
not yet fully understood. Too, how the initial, altered form (disease form) enters the
bloodstream and eventually enters the cells of the brain is also unknown. In this
regard, a possible receptor in the membrane of cells that line the intestine may have
been found that could bind, transport and eventually allow the protein to enter the
bloodstream.
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