As
nineteenth century microbiologists worked to isolate causative agents of
various diseases, in some cases they found that they seemed to be unable to
find an associated microbe to grow in lab media. However, they could filter infectious
material from one host through a filter designed to trap bacteria, and then use
the filtered material to cause the disease in a healthy susceptible animal.
Some believed that the fluid itself (no agent) somehow caused the disease.
Others believed that these causative agents must be very tiny bacteria, but
still others suspected that a completely different pathogen was involved.
Pasteur called this unknown agent by the name virus, meaning Latin for poison.
Often, because whatever it was could pass through filters, it was called a
filterable virus.
In
the early 1892, a virus was proved to cause a plant disease, tobacco mosaic
disease. The first animal disease proved to be caused by a virus was foot and
mouth disease in 1898. In 1901, Walter Reed proved that a virus was responsible
for a human disease, yellow fever.
We
now know that many diseases of plants, domestic animals and humans are caused
by viruses. We probably have not yet identified all viruses that affect humans.
Several newly discovered viruses include SARS virus, HIV (AIDS virus),
Hantavirus in the form that occurs in the American Southwest, Venezuelan
hemorrhagic fever, and Ebola fever
virus.
Viruses
open up a debate on exactly what constitutes a living entity. Arguments that
viruses are never alive:
1. No metabolic activity outside a living
cell
2. Reproduction only inside living
cells---but this is also true for chlamydias, for
example, and nobody doubts that they
are alive
3. Have only a single type of nucleic acid
(DNA or RNA) but never both, as all living
things would have
Arguments
that viruses are at least sort of alive:
1. Inside cells, viruses multiply, using
the synthesis machinery of the cell
2.
Viruses do have either RNA or DNA---only living things would have any
nucleic acid at all
3. Viruses carry genes in their nucleic
acid that cause the synthesis of specialized viral
proteins—only something alive would
have its own genes
4. Viruses are able to cause infectious
disease
This
is not an argument with a definite answer. We do know that all of the above
facts are true about viruses, whether they prove alive or dead or not. Viruses
can be described as obligate intracellular parasites with the following
characteristics:
1. Contain a single type of nucleic acid,
RNA or DNA, but never both
2. Contain a protein coat, and sometimes a
membrane-like envelope, that encloses the nucleic acid
3. Multiply inside living cells, after
taking over the synthesis machinery of the cell
4. Cause the synthesis of specialized
structures that can transfer the viral nucleic acid to other cells
Since
so much of the activity due to the virus involves use of the cell’s own
processes, this makes it very difficult to find antibiotics that damage the
virus but not the host cell.
Most
viruses are fairly specific as to what species they are capable of infecting.
Most are limited to only one species or several closely related species. There
are even viruses that attack only bacteria. These are known as bacteriophages,
or just phages.
The
main factors in determining host range are:
1. The requirements of the virus for
specific attachment sites on the host cell. The outer surface of the virus must
interact with specific receptor sites of the surface of the host cell. These
receptor sites will be on the plasma membranes of animal cells and on the cell
wall, fimbriae or flagella of a bacterium.
2. The availability within the cells of the
potential host of the cellular factors required for viral multiplication.
All
viruses are small, so small that electron microscopes are needed to view them.
A few of the very largest viruses are roughly the same size as the very
smallest of bacteria. Viruses are measured in nanometers. To refresh your memory:
Centimeter (cm) = 0.01 meter (2.54 cm = 1 inch)
Millimeter (mm) = 0.001 meter (25.4 mm = 1 inch)
Micrometer (mm) = 0.001 mm (25,400 mm = 1 inch)
Nanometer (nm) = 0.001 mm
(25,400,000 nm = 1 inch)
Viruses
range from 20 to 1000 nanometers in length.
A
virion is a complete infectious virus particle. It consists of a nucleic acid
surrounded by a protein coat, which protects the nucleic acid and aids in
transmission. The structure of the outer coat may be used in classification.
Viruses
contain only one kind of nucleic acid, either RNA or DNA. To make things confusing, this nucleic acid
may not be exactly the same in structure as the nucleic acid of cells. In
viruses, RNA is not always single-stranded; it may be a double strand. DNA is
not always double-stranded; it may be a single strand. The nucleic acid may be
linear or circular, or even in several segments. The amount varies from a few
thousand nucleotides up to 250,000 nucleotides.
CAPSID
AND ENVELOPE
The
nucleic acid is surrounded by a protein coat called the capsid. The capsid is
composed of protein subunits called capsomeres. The structure of these viral
proteins is determined by genes of the virus. The arrangement of the capsomeres
is characteristic of the virus. With the electron microscope, individual
capsomeres may be visible.
Some
viruses have an additional outer covering called an envelope. This is composed
of lipids, proteins, and carbohydrates. If a virus has this covering, it was
acquired as the virion was released from an animal host cell. The envelope is
basically plasma membrane of the host cell, but the proteins it contains are
viral proteins.
In
some enveloped viruses, the envelope is covered by carbohydrate-protein
projections called spikes. These project from the surface of the envelope and
may be used by the virus to attach to host cells. The spikes can be used for
identification, and they also enhance the pathogenicity of some viruses. For
example, the virus that causes influenza has spikes that bind to red blood
cells and cause them to clump together (hemagglutination).
Nonenveloped
viruses do not have the envelope. In these the capsid provides the protection
for the nucleic acid and attaches to host cells.
Whether
the outer covering of a virus is an envelope or the capsid, it is this outer
covering to which the immune system of the host responds by producing
antibodies, which should be capable of binding to and inactivating the virus.
Some viruses slip past this defense by frequently changing the characteristics
of their outer covering so that the antibodies no longer recognize it. Influenzavirus
is outstanding at this trick, and this is why flu shots have to change every
year.
Based
on the plan of their capsids, viruses are placed in several categories:
1. Helical viruses---these are like rods and
may be rigid or flexible. The capsid has
a helical (spiral) structure. Rabies virus and Ebola virus are examples.
2. Polyhedral viruses---many-sided
viruses---most of these have a capsid in the shape of an icosahedron, which has
20 triangular faces. Examples of this are poliovirus and adenovirus.
3. Enveloped viruses---these have an
envelope covering the capsid and mostly are somewhat spherical. If not
spherical, the virus could be called enveloped helical (such as influenza
virus) or enveloped polyhedral (such as
herpes virus)
4.
Complex viruses---these don’t fit into the above categories. Many of them are
bacteriophages. Fig. 13.5 P. 391 shows an example of a bacteriophage with a
polyhedral head and a helical tail sheath.
Pox -viruses are also in this group. They do not have clearly identified
capsids but do have layers of protein around the nucleic acid.
Viral
classification is needed for the same reasons we need to classify bacteria and
other organisms, but a perfect system that fits all needs has yet to be
developed. Early classification sorted out viruses based on the symptoms they
produced. Since this can vary, this system was not satisfactory, especially as
more and more viruses were discovered. In 1966 the International Committee on
the Taxonomy of Viruses was formed. As the system now operates, here are the
main features:
1. Viruses are grouped into families based
on:
a. Nucleic acid type
b. Strategy for replication
c. Morphology
2.
Genus names end in ---virus
3.
Family names end in ---viridae
4.
Order names end in ---ales
A
viral species is a group of viruses sharing the same genetic information and
ecological niche. Species are designated by descriptive common names (such as
human immunodeficiency virus = HIV) , and if there are subspecies they are
designated by a number (HIV-1). Table 13.2 P. 392- 393 is a summary of the
classification of viruses that infect humans.
Viruses
grow only in living cells, so regular lab media are not suitable. This plus the
fact that many viruses are host specific complicates the job of cultivating
viruses. The viruses that attack bacteria (bacteriophages) are the ones that
have been studied the most.
Phages
can be grown in liquid bacterial cultures or in bacterial cultures on solid
media. The bacteriophages were discovered by accident when a liquid culture of
bacteria in a lab was accidentally invaded by bacteriophages. Liquid cultures
become quite cloudy as the numbers of bacteria increase, but to the
researcher’s surprise, a culture that was very cloudy and full of bacterial
growth one day was perfectly clear the next. If a little of this clear solution
was added to another cloudy culture, the same thing happened. Finally it was
discovered that a virus was attacking the bacteria and causing them to lyse
(burst open).
If
a count of the number of phage particles present is needed, solid media should
be used. A pour plate is done by adding bacteria and a measured amount of a
liquid containing phages to liquid agar and pouring it into a sterile Petri
dish. Enough bacteria are included that without interference they would form a
solid filmy growth across the entire surface of the agar (bacterial lawn). In
every spot where a phage particle landed, the bacteria will be lysed and a
small clear area called a plaque will appear. These can be counted. The number
of viruses in the original viral suspension is also described as the number of
plaque-forming units.
Three
methods are used:
1. Living animals
a. Some animal viruses can be cultured
only in living animals. Finding an experimental animal in which the virus will
grow can sometimes be difficult. In studying human viruses and also in
developing vaccine against them, this is especially true.
b. Studies of the immune system’s
response to the virus can only be done in a living infected animal.
c. Animals can be inoculated in an effort
to diagnose a disease
2. Embryonated eggs---a hole is drilled in
the shell of a fertile egg and the virus is injected into the most appropriate
part of the developing chick. The hole is sealed. If the virus grows, the chick will die or
show damage, or lesions will form on the membranes.
a. This method is currently used in
production of some vaccines.
b. When this method was developed, it was
the only alternative to a lab animal. Other than vaccine production, it has
mostly been replaced by tissue cultures.
3. Cell cultures (tissue cultures)---this is
now the growth method of choice for viruses if the virus will grow this way and
if the work can be done by this method. A small piece of animal tissue is split
into individual cells by an enzyme. The cells are placed in a solution that
provides oxygen, nutrients, etc.---all the requirements for growth. Normal
cells tend to divide and form a single layer over the surface of a glass or
plastic container. Viruses growing in these cells tend to cause infected cells
to deteriorate-----this is called cytopathic effect (CPE). It can be observed
and the number can be counted.
a. Primary cell lines are derived from
normal tissues and usually die out after a few generations.
b. Diploid cell lines are developed from
human embryos and will usually divide about 100 times. These can be used for
some viruses that require human cells.
c. Continuous cell lines are derived from
cancer cells. These cells are said to be transformed and will live and divide indefinitely. The most famous of these, the HeLa line, originated from a cervical cancer in 1951,
and the cells are still going strong.
Not
all viruses can be grown in cell cultures. This technique is quite complicated
and is usually performed in central laboratories that specialize in such work.
This
is not an easy job. Although some
viruses have a characteristic appearance, an electron microscope is required to
see them. Most identification of viruses is done through serological work that
involves identification of a virus by its reaction with specific
antibodies. Sometimes the effect of a
virus on host cells can be observed and this can contribute to identification. Study of nucleic acids is also a possible
means of identification.
Every
virus carries genes that code for viral proteins, which include the capsid
proteins and other structural components as well as any enzymes needed for the
replicating or processing of viral nucleic acid. Enzymes needed for protein
synthesis, ribosomes, tRNA, and energy are taken from the host cell and put to
use by the virus. Some virions carry a few preformed enzymes into the cell as
they enter. Other viruses do not contain any preformed enzymes, only the genes
for making any enzymes they will need that the host cell does not provide.
The
basic mechanism for viral multiplication is similar for all viruses. We have
the best understanding of life cycles of the bacteriophages. Once a phage has
entered a cell, there are two possibilities for the next steps. These are known
as the lytic cycle and the lsyogenic cycle. The best understood phages are the
ones called T-even phages of Escherichia
coli, and these are used as examples.
1. The lytic cycle---in this cycle, the virus multiplies within
the host cell, which then dies and releases the new viral particles. This
occurs in 5 steps:
a. Attachment---the phage and the susceptible bacterial
cell accidentally bump into each other. An attachment site on the virus
attaches to a complementary receptor site on the bacterial cell wall. Weak
chemical bonds are formed between the attachment site and the receptor
site. This is called attachment or
adsorption.
b. Penetration---the bacteriophage injects its DNA into
the bacterium. To do this, the phage’s tail releases an enzyme, phage lysozyme,
which breaks down an area of the bacterial cell wall. The tail sheath of the
phage contracts and pushes the tail core through the cell wall. When the tip of
the core reaches the plasma membrane, the DNA comes through the tail and enters
the bacterial cell. The capsid remains outside.
c. Biosynthesis---first the virus stops host protein
synthesis by breaking up the host DNA, directing the production of viral
proteins which interfere with transcription of host DNA, or repressing
translation of host cell mRNA. Then the
phage uses nucleotides and enzymes of the host cell to synthesize many copies
of the phage DNA. If any phage enzymes are required for this to proceed, these
are synthesized and are called early proteins.
After
this, biosynthesis of other viral proteins begins. mRNA is transcribed from phage DNA so that
any additional phage enzymes and capsid proteins can be synthesized. These are
called late proteins.
There
is a period during which no complete phage particles are present---only the
phage DNA and components of the capsid, not yet assembled. This is called the
eclipse period.
d. Maturation---bacteriophage parts are assembled into
complete virions. This assembly occurs spontaneously, without requiring any
special enzymes or proteins to do the job. The phage heads and tails are
assembled, the head is filled with phage DNA, and attached to the tail.
e. Release---this stage is also called lysis. The newly
assembled virions are released as the plasma membrane and cell wall break open,
due to the action of phage lysozyme which has been synthesized in the cell.
These new bacteriophages find other bacterial cells nearby and start the cycle
again.
The
time that elapses from attachment to release is called the burst time and
averages 20 - 40 minutes. The number of new phages produced from a single cell
is called the burst size, and usually ranges from 50 - 200. (We will find that animal viruses produce
many more new viruses in a cycle, but remember animal cells are much bigger.)
2. Lysogenic cycle---also known as lysogeny. Some viruses do
not always cause lysis and death of the host cell right away. Some are able to
undergo a cycle in which they integrate their DNA into the chromosome of the
host cell. Phages that behave this way are called lysogenic, avirulent, or
temperate phages. Bacterial host cells
affected this way are called lysogenic cells.
Steps:
a. Penetration occurs as described
b. The linear phage DNA forms itself into
a circle
c. At this point there are 2
possibilities:
(1) This circle of DNA can multiply
and be transcribed. If this happens, new phage particles will be produced and
the cell will be lysed. This is the lytic cycle as already described.
(2) Another possibility is that the
circle of phage DNA will be spliced into the bacterial chromosome. If this is
to occur, two phage genes will be transcribed right away and two repressor
proteins will be made by the machinery of the host cell. These repressor
proteins will prevent the expression of the rest of the phage genes. While the
phage DNA is inserted into the host chromosome, it is known as a prophage. Each
time the host cell divides, the phage genes are replicated along with the rest
of the chromosome and passed on to all daughter cells. Effects:
(a) The host cell is immune to
infection by another one of the same phage.
(b) Phage conversion—the host cell
may exhibit new properties. The genes carried by the phage may allow host cell
to produce a toxin that is otherwise cannot. Bacteria that are pathogenic only
due to the presence of a prophage include Corynebacterium
diphtheriae, Clostridium botulinum, Vibrio cholerae, and the strain of Streptococcus that causes scarlet fever.
(c) Specialized transduction
becomes possible. Certain bacterial genes can be transferred this way. Each kind of lysogenic phage has a certain
spot in the bacterial chromosome where it always inserts itself. If this phage
later detaches from the host cell chromosome it may take the bacterial genes
next to it on the chromosome with it. Since the phage is always in the same
part of the chromosome, the genes it takes with it are constant also. The phage
then enters a regular lytic cycle, and each copy of phage DNA that is made
contains the bacterial genes along with the phage genes. When resulting new
phages invade other cells, they take the
bacterial genes in. The change from lysogeny to the lytic cycle may be
triggered by UV light or certain chemicals, or it may occur spontaneously.
A
process similar to this can occur with a few animal viruses. The viral genes
may be spliced into a chromosome or remain separate. This is called a latent
infection.
This
process follows the same basic pattern as bacteriophage multiplication, but
there are several differences. Here is
a brief comparison:
|
STAGE |
BACTERIOPHAGE |
ANIMAL VIRUSES |
|
ATTACHMENT |
TAIL FIBERS
ATTACH TO CELL WALL PROTEINS |
ATTACHMENT SITES
ARE PLASMA MEMBRANE PROTEINS AND GLYCO-PROTEINS |
|
PENETRATION |
VIRAL DNA
INJECTED INTO HOST CELL |
CAPSID ENTERS BY
ENDOCYTOSIS OR FUSION |
|
UNCOATING |
NOT REQUIRED |
ENZYMATIC REMOVAL
OF CAPSID PROTEINS |
|
BIOSYNTHESIS |
IN CYTOPLASM |
IN NUCLEUS (DNA
VIRUSES) OR CYTOPLASM (RNA VIRUSES) |
|
CHRONIC INFECTION |
LYSOGENY |
LATENCY; SLOW
VIRAL INFECTIONS; CANCER |
|
RELEASE |
HOST CELL LYSED |
ENVELOPED VIRUSES
BUD OUT; NONENVELOPED VIRUSES RUPTURE PLASMA MEMBRANE |
The
following section discusses the action of animal viruses in more detail. Both
RNA and DNA viruses share most of these processes, but the process of
biosynthesis differs, as does the process of viral release.
1. Attachment-----animal viruses must find complementary
receptor sites on the surface of the host cell. These receptor sites will be
proteins and glycoproteins of the plasma membrane. The attachment sites of the
virus are distributed over the surface of the virus. These may vary somewhat
among different viruses, some being small fiber-like structures and some being
spikes of the envelope.
Receptor
sites are inherited characteristics of the host. The number of receptors and
even whether there are any receptors at all for a particular virus can vary
from person to person. If there are no complementary receptors, the cell is
immune to that particular virus. There is a possibility that treatments may be
developed that block either viral attachment sites or receptor sites on cells,
which would prevent infection by the virus.
2. Entry-----viruses often enter a cell by
pinocytosis, a process intended to bring in nutrients and other required
molecules. The virion attaches to a small outfolding of the plasma membrane and
the plasma membrane responds by bringing the virion in, enclosed in a vesicle.
Once the virion is enclosed within a vesicle, its viral envelope (if present)
is destroyed. The capsid is digested when the cell tries to digest the contents
of the vesicle, or the nonenveloped capsid may be released into the cytoplasm
of the host cell.
Enveloped
viruses can enter by an alternative method called fusion. The viral envelope
fuses with the plasma membrane and releases the capsid into the cytoplasm.
3. Uncoating-----this is the separation of the viral
nucleic acid from its protein coat. This process is not well understood and
varies among different viruses.
a.
Some are uncoated by lysosomal enzymes of the host cell inside the
phagocytic vesicle
b. Poxviruses carry the gene for a
special enzyme to uncoat them
c.
Most other viruses are uncoated by enzymes in the cytoplasm of the host
cell
1.
Early
a. Destroy host cell DNA and take over
control of the cell
b. Transcription and/or translation of viral
enzymes needed for multiplication of the viral nucleic acid
c. Make many copies of the viral GENOME (RNA
or DNA)
2.
Late
a. Make mRNA for viral PROTEINS and
synthesize these proteins (for capsid, etc.)
b. Assemble new virions--anywhere from
several thousand to a million
1. DNA virus nucleic acid enters the nucleus of
the host cell and is replicated there, using viral enzymes. 2. The capsid and
other proteins are synthesized in the cytoplasm, using host cell ribosomes and
enzymes.
3.
These proteins then migrate into the nucleus and are joined with the newly
synthesized DNA to form virions, which are then released from the host cell.
Poxviruses
are an exception to this; all their components are synthesized in the
cytoplasm.
1. Adenoviridae---named for the adenoids,
where they virus was fist isolated. Causes acute respiratory disease such as
the common cold.
2. Poxviridae---diseases causing skin
lesions such as smallpox and cowpox and that is where the name came from (pox =
pus-filled lesion). Viral multiplication is started by viral transcriptase
(-----ase name = enzyme). Viral components are synthesized and assembled in the
cytoplasm.
3. Herpesviridae-----named for the spreading
(herpetic) appearance of cold sores. There are nearly 100 herpesviruses. (HHV
means human herpes virus.)
a. HHV-1 and HHV-2 cause cold sores and
genital herpes
b. HHV-3 which causes chickenpox
c. HHH-4, also known as Epstein-Barr
virus---causes infectious mononucleosis
d. HHV-5 also known as Cytomegalovirus
e. HHV-6 also known as Roseolovirus
f. HHV-7 infections of infants causing
rash
g. HHV-8 Kaposi’s sarcoma in AIDS
patients
4. Papovaviridae---named for some of the
things this family causes-----papillomas (warts), polyomas (tumors), and
vacuoles (cytoplasmic vacuoles produced by some of these viruses). Papillomavirus causes warts. Some of the
Papillomavirus species (genital warts, for example) can transform cells and
cause cancer. Viral DNA is replicated in
the host cell nucleus, along with host cell chromosomes. Papovaviruses are often used as an example of
multiplication of a DNA virus.
5. Hepadnaviridae---named because they
cause hepatitis and they are DNA viruses. The only genus in this family causes
hepatitis B. (All the other forms of hepatitis are caused by RNA viruses.)
These viruses are different because they synthesize DNA by copying RNA, using
the viral enzyme reverse transcriptase, which will be discussed later.
BIOSYNTHESIS
OF RNA VIRUSES
Since
these viruses have RNA as their only nucleic acid, their mechanisms of mRNA
formation must differ from those used to make mRNA using DNA as the template.
RNA viruses multiply in the host cell’s cytoplasm. The major differences among
the multiplication processes of these viruses are the ways mRNA and copies of
the viral RNA are produced.
1. Picornaviridae---these are the smallest
viruses and are named with the prefix
pico--- (meaning small) plus RNA. Poliovirus is an example.
2. Togaviridae---this group of enveloped
viruses includes alphaviruses and arboviruses.
Rubella virus is an example.
3. Rhabdoviridae---these are usually
bullet-shaped and include the rabies virus.
4. Reoviridae--- these are found in the
respiratory and enteric (digestive) tracts of humans. Rotavirus is an example.
5. Retroviridae-----this group includes the
virus that causes AIDS (HIV-1 and HIV-2) as well as some viruses that cause
cancer. These viruses form mRNA and RNA for new virions as follows:
a. They carry their own polymerase
enzyme, an RNA-dependent RNA polymerase called reverse transcriptase.
(Host cells have only DNA-dependent RNA polymerase.)
b. Reverse transcriptase uses the RNA of
the virus to synthesize a complementary strand of DNA.
c. This single strand of DNA is used to
form a complementary strand, producing double-stranded DNA.
d. The original virus RNA is broken
down.
e. The new DNA is integrated into a
chromosome of the host cell. In this state, spliced into a chromosome, the
viral DNA is called a provirus. The provirus may remain inactive for long
periods of time. If the host cell divides, each daughter cell receives a copy
of the provirus along with the normal genes.
f. The provirus may become active and
be transcribed, resulting in the production of new virus particles.
g. Another possibility is that the
provirus can convert the host cell into a cancer cell.
The
assembly of the capsid usually occurs spontaneously when all components have
been synthesized. If the virus is an enveloped virus, the viral proteins to be
included in the envelope are synthesized in the host cell along with the rest
of the viral proteins. These proteins are then incorporated into the plasma
membrane of the host cell and added to the lipids and carbohydrates already
produced by the host cell for its own use. The new virions leave the cell by
budding, each pushing out a small section of the membrane and popping out of
the cell, completely wrapped in that bit of plasma membrane. The host cell can
live for at least a while during this process, and occasionally a host cell
survives.
Nonenveloped
viruses cause lysis of the host cell. The plasma membrane ruptures and new
virions leave through the opened area. This results in immediate death for the
host cell.
VIRUSES
AND CANCER
Some
specific types of cancer are caused by viruses. This was first discovered early
in the twentieth century when viruses causing leukemia in chickens and then a
chicken sarcoma virus were found. In 1936, a virus was proved to cause
adenocarcinomas of the mammary glands in mice. The first oncovirus (cancer-causing
virus) in humans was isolated in 1972 from a human sarcoma.
Difficulties
in recognizing viral causes of cancer are due to:
1. Most cells invaded by oncoviruses do NOT
become cancerous.
2. Cancer might not develop until years
after the viral infection
3. Cancers do not seem to be contagious, as
viral diseases usually are.
4. If the virus causes a cancer that affects
only humans, people cannot be used to test the theory.
TRANSFORMATION
OF NORMAL CELLS INTO TUMOR CELLS
Anything that alters the genetic material of a cell has the
potential to change a normal cell into a cancer cell. The parts of the genome
this affects are genes known as oncogenes. Viruses capable of inducing tumors
are called oncogenic viruses. They probably account for around 10% of human
cancers. Genetic material of oncoviruses integrates into the host cell’s DNA
and replicates along with the host cell chromosomes. Cells that have been
changed to tumor cells are said to be transformed.
1.
Transformed cells tend to divide in an uncontrolled rapid way.
2.
They tend to have chromosome abnormalities and possibly a different shape than
normal cells.
3.
They lose the characteristic of contact inhibition. This means that instead of
forming a single layer of cells when grown in tissue culture, transformed cells
tend to form tumor-like masses of cells piled up on each other.
4.
Transformed cells may cause tumors when injected into susceptible animals.
5.
Many tumor cells that have been transformed by viruses display a virus-specific
antigen on their surface called tumor-specific transplantation antigen (TSTA)
or an antigen in the nucleus called the T antigen.
Several
families of DNA viruses contain oncoviruses.
1. Papovaviridae---papilloma viruses cause
uterine and cervical cancer
2. Herpesviridae---Epstein-Barr virus causes
infectious mononucleosis and two human cancers, Burkitt’s lymphoma and
nasopharyngeal carcinoma. It may possibly also be involved in Hodgkin’s
disease. Most people carry this virus, but very few of them go on to develop
cancer.
3. Hepadnaviridae---the hepatitis B virus
probably causes most cases of primary liver cancer.
The only RNA viruses known to cause cancer are
members of the family Retroviridae.
1. Human T-cell leukemia viruses (HTLV-1 and
HTLV-2) cause adult T-cell leukemia and some lymphomas in humans.
2. Sarcoma viruses of cats, chickens,
rodents and mammary tumor viruses of mice are retroviruses that are oncogenic.
3. Feline leukemia virus is also a
retrovirus that causes a transmissible leukemia in cats.
Retroviruses
are RNA viruses, but they use reverse transcriptase to produce double-stranded
DNA which integrates into a chromosome of the host cell. These viruses may
contain oncogenes themselves or turn on host cell oncogenes or other
cancer-causing factors.
Some
viruses can remain in the host for long periods of time without causing
disease. For example, all human herpesviruses can remain in host cells
throughout the lifetime of the individual. At some point the virus many become
active. This is called a latent infection. The virus that causes cold sores
(fever blisters) inhabits the host’s nerve cells but causes no damage until a
fever or a sunburn activates it.
Chickenpox
virus also can exist as a latent infection. Following a childhood case of
chickenpox, some of the virus reaches nerve cells and remain latent. Later,
changes in the immune response or possibly other factors may activate the
virus, causing shingles.
This
term refers to a viral infection that occurs gradually over a long period of
time. The virus is gradually building up over a long period of time, and in
most cases eventually will be fatal. These infections can also be called slow
viral infections. An example is that very rarely, years after causing a normal
case of measles, the virus remains in the body and eventually causes a rare
form of encephalitis.
These
are strange infectious agents which appear to be proteins. The first disease
identified to be of this type was scrapie of sheep in 1982. There are now nine
animal diseases in this category, including mad cow disease. All of them are
neurological diseases causing the development of large vacuoles in the brain,
and can be called spongiform encephalopathies. The best known ones that affect
humans are kuru and Creutzfeldt-Jakob disease. These diseases seem to run in
families, which may indicate a genetic component, but they also can be
transmitted from person to person.
Somehow
these prions, which appear to be pure protein with no nucleic acid involved,
may change a normal gene found in brain cells to an abnormal form. Exactly how
this takes place or even exactly how the damage occurs is not yet understood.
One hypothesis is that the prion enters, reacts with a normal protein and changes its shape. They
the newly changed abnormal proteins react with additional normal proteins and
change their shape--on and on.
Many
viruses exist that infect plants instead of animals and bacteria. They are
similar to animal viruses in many ways, and cause damage to crops and gardens.
Plant viruses must find a way to enter plant cells through the cell wall. Often
insects transmit these viruses from plant to plant, chewing or otherwise
penetrating the cell wall to let the virus inside. Pollen and seeds of infected
plants may carry the virus.
Some
plant diseases are caused by viroids.
These are pieces of naked RNA about 300 - 400 nucleotides long. They do not
have a protein coat. The RNA does not code for proteins, but somehow causes
disease in infected plants and can spread from plant to plant.