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Aids
The
causative agent of AIDS
is HIV, a human retrovirus.
Researchers have known since
1984 that HIV enters human
cells by binding with a
receptor protein known as CD4,
located on human immune-cell
surfaces. HIV carries on its
surface a viral protein
known as gp120, which
specifically recognizes and
binds to the CD4 protein
molecules on the outer surface
of human immune cells.
However, in 1984 researchers
found that CD4 by
itself was not sufficient for
HIV infection to take place.
Some other unknown factor,
found only in human cells, was
also required. After much
research, in 1996 scientists
discovered that HIV must also
bind to chemokine
receptors, small proteins also
found on the surface of human
immune cells, to enter the
cells. The first chemokine
receptor linked to HIV entry
was CXCR4 (originally
called fusin), which is bound
by HIV strains that dominate
during the latter stages of
the disease. Researchers then
determined that another
chemokine receptor, CCR5,
bound HIV strains that
dominate in the early stages
of the disease. Researchers
are continuously discovering
more chemokine receptors.
Any human
cell that has the correct
binding molecules on its
surface is a potential target
for HIV infection. However, it
is the specific class of human
white blood cells called CD4
T-cells that are most affected
by HIV because these cells
have high concentrations of
the CD4 molecule on
their outer surfaces. HIV
replication in CD4
T-cells can kill the cells
directly; however, the cells
also may be killed or rendered
dysfunctional by indirect
means without ever having been
infected with HIV. CD4
T-cells are critical in the
normal immune system because
they help other types of
immune cells respond to
invading organisms. As CD4
T-cells are specifically
killed during HIV infection,
no help is available for
immune responses. General
immune system failure results,
permitting the opportunistic
infections and cancers that
characterize clinical AIDS.
Although it
is generally agreed that HIV
is the virus that causes AIDS
and that HIV replication can
directly kill CD4
T-cells, the large variation
among individuals in the
amount of time between
infection with HIV and a
diagnosis of AIDS has led to
speculation that other cofactors—that
is, factors acting along with
HIV—may influence the course
of disease. The exact nature
of these cofactors is
uncertain—it is believed
that they may include genetic,
immunologic, and environmental
factors or other diseases.
However, it is clear that HIV
must be present for the
development of AIDS.
Cold Sore
Cold Sore ,
also called fever blister, a
small, painful blister on the
face, especially around the
lips and nose and inside the
mouth. A cold sore first
appears as a small red pimple
that gradually develops into a
small, painful blister full of
clear fluid. When the blister
ruptures, it appears
yellowish, dry, and crusted. A
herpes simplex virus causes
cold sores. They spread from
one individual to another by
direct contact between skin
surfaces, and they usually
erupt in clusters.
Most people
infected by the herpes simplex
virus contract it before
adolescence, but only a small
percent of exposed children
actually develop symptoms at
that time. When the herpes
simplex virus is inactive, it
lies dormant in neurons, or
nerve cells. Later, illnesses
or emotional upsets can
reactivate the virus and
trigger the development of
cold sores, and affected
individuals often suffer from
recurring attacks. Cold sores
tend to accompany common colds
and infectious diseases, such
as pneumonia and diphtheria
that are characterized by
fever. The cold sore infection
itself can raise body
temperature above normal and
account for swelling in the
lymph nodes of the neck. Cold
sores usually last from ten
days to two weeks, and no
preventive measures are known,
although antibiotic ointments
can control complications
caused by the bacterial
infections that often
accompany cold sores. The
antiviral ointments known as
vidarabine and acyclovir may
also be prescribed to relieve
the pain of cold sores.
Diarrhea
Diarrhea,
Frequent
passage of abnormally loose,
watery stool. Diarrhea usually
develops suddenly and may last
from several hours to a few
days. It is often accompanied
by abdominal pains, low fever,
nausea, and vomiting. If the
attacks are severe or
increasingly frequent,
exhaustion and dehydration can
result. In normal digestion
the large intestine absorbs
excess water from liquid food
residues produced by earlier
phases of the digestive
process before excreting
semisolid stools. When the
mucous membrane lining the
large intestine is irritated o
r inflamed, food residues move
through the large intestine
too quickly and the resulting
stool is watery because the
large intestine cannot absorb
the excess water.
Diarrhea is
not a disease. It is a symptom
of numerous disorders, such as
food poisoning from
contaminated foods or
beverages, infections by
viruses and bacteria, or
anxiety. Chronic diarrhea,
which lasts weeks or months,
may be caused by amoebic
dysentery (intestinal
infection), tumors, and other
serious intestinal disorders
such as Crohn’s
disease,
ulcerative
colitis,
or irritable
bowel syndrome.
Except in the case of
irritable bowel syndrome, the
stool may contain blood or
pus.
The usual
treatment for diarrhea
consists of bed rest, drinking
liquids to replace fluids and
salts lost from the body, and
eating soft foods. Dehydration
is a serious concern in
infants and the elderly. If
the condition lasts more than
a few days, a physician should
be consulted.
Red
Blood
Red blood
cells are formed in the bone
marrow (see Bone).
After an average life of 120
days, red blood cells are
broken down and removed by the
spleen.
The different kinds of white
blood cells are formed in
various sites: neutrophils,
basophils, and eosinophils
(the granular leukocytes) are
formed in the bone marrow;
lymphocytes are formed in the thymus,
the lymph glands (see Lymphatic
System),
and other lymphatic tissue;
and monocytes are formed in
the spleen, liver,
lymph nodes, and other organs.
Platelets are formed in the
bone marrow. All these
constituents of the blood are
continuously worn out or
consumed and must be
continuously replaced.
The
components of plasma are
formed in various organs of
the body. The liver makes
albumin and fibrinogen, stores
blood sugar, and releases such
important elements as sodium,
potassium, and calcium;
endocrine glands (see Endocrine
System)
make the hormones that are
transported in the plasma; the
lymphocytes and plasma cells
make some of the proteins; and
other constituents are derived
by absorption from the
intestinal tract (see Intestine).
Coagulation
One of the
most remarkable properties of
blood is its ability to clot,
or coagulate. Normally, within
the blood vessels, blood
remains in a fluid condition.
Within the body, blood may
clot in response to tissue
injury, such as a muscle tear,
a cut, or a sharp blow. When
exposed to air, blood becomes
sticky and sets into a firm,
jellylike mass. This mass then
separates into two portions: a
firm red clot floating free in
a transparent, straw-colored
fluid called serum.
A clot
consists almost entirely of
red blood cells entangled in a
network of fine fibrils, or
threads, composed of a
substance called fibrin.
Fibrin does not exist as such
in blood but is created by the
action of thrombin, an enzyme
that promotes the conversion
of fibrinogen, one of the
plasma proteins, to fibrin in
the clotting process. Thrombin
is not present in circulating
blood; it is formed from
prothrombin, another of the
plasma proteins, by a complex
process involving blood
platelets, certain calcium
salts, substances produced by
injured tissue, and contact
with rough surfaces. If any of
these factors is deficient,
clot formation is defective.
The addition of sodium citrate
removes calcium ions from the
blood and thus prevents a clot
from forming. Lack of vitamin
K makes impossible the
maintenance of the proper
amount of prothrombin in the
blood. Certain diseases may
lower the concentration of the
various clotting proteins or
of the platelets of the blood.
Homeostasis
Certain
blood characteristics are kept
within narrow limits by
precisely regulated processes
that maintain a state of
equilibrium, or homeostasis.
For example, the alkalinity of
the blood is so nearly
constant that if the pH
falls to 7.0 (the same as that
of pure water), the individual
lapses into an acidotic coma
that may be fatal; on the
other hand, if the pH rises
above 7.5 (the same as that of
a solution containing 1 part
of caustic soda in 50 million
parts of water), the
individual lapses into tetany,
a condition marked by muscle
spasms, and will probably die.
Similarly, a fall in blood
sugar concentration, normally
about 0.1 percent, to less
than 0.05 percent brings on
convulsions. Persistently high
concentrations of blood sugar,
when accompanied by a variety
of important metabolic
changes, often bring about
diabetic coma (see Diabetes
Mellitus).
The temperature of the blood
in a normal individual does
not vary more than 0.6° C
(1° F) from a normal average
of 37° C (98.6° F). A rise
in blood temperature of 3.3°
C (6° F) is usually an
indication of serious illness,
and a rise of 6° C (10° F)
generally causes death.
Blood
Diseases
Disorders
of the blood arise from
abnormal changes in its
composition. A laboratory
technique known as complete
blood count (CBC) is a useful
indicator of disease and
health. A precisely measured
sample of blood is
automatically diluted, and an
electronic or optical scanner
counts the cells, usually.
Different settings or diluting
agents permit the counting of
red cells, white cells, or
platelets. A CBC may also
include a sorting of white
cells into categories, which
may be done visually from a
stained sample on a microscope
slide or automatically using
one of several techniques.
An abnormal
reduction in the hemoglobin
content or in the number of
red blood cells is known as anemia,
which is regarded as a symptom
rather than a disease and has
a number of causes. Probably
the most common cause is blood
loss, or hemorrhage.
Excessive destruction of the
red blood cells, a condition
known as hemolytic anemia, may
be caused by a variety of toxins
or by an antibody to the red
blood cells. One type of
anemia, occurring in infants
at or shortly before birth is
erythroblastosis fetalis, or
Rh disease (see Rh
reason).
Anemia also
results from decreased
production of red cells,
attributable to a loss of
iron, to a deficiency of
vitamin B12, or to a failure
in the function of bone
marrow. Finally, one group of
anemias is caused by inherited
defects in the production of
red cells or hemoglobin. These
anemias include a number of
hereditary disorders in which
the red cells lack any one of
several enzymes needed if the
cell is properly to utilize glucose.
Formation
of abnormal hemoglobin is
responsible for the hereditary
defects called sickle-cell
anemia
and thalassemia major. Both
are severe diseases that can
be fatal in childhood.
An increase
in the number of circulating
red blood cells is called
polycythemia, which can be a
primary condition or one that
follows decreased oxygenation
of the blood, or hypoxia.
Extreme hypoxia occurs most
commonly in advanced lung
disease, in certain types of
congenital heart disease, and
at high altitudes.
Leukemia
is accompanied by a disordered
increase in white blood cells.
Several types of leukemia
exist, each characterized by
the cells involved.
A
deficiency in any of the
factors necessary for blood
coagulation leads to excessive
bleeding. A decrease in
platelets is known as
thrombocytopenia; a decrease
in clotting factor VIII
results in hemophilia A
(classic hemophilia); a
decrease in clotting factor IX
results in hemophilia B,
commonly known as Christmas
disease. Several of the
hemorrhagic diseases, such as
hemophilia, are hereditary.
Preparations are available
that contain some of the
clotting factors in
concentrated form for treating
some of these disorders. In
1984 researchers developed a
genetic engineering technique
for making Factor VIII, a
blood-clotting factor of vital
importance for victims of the
most common form of
hemophilia. Commercial
production of Factor VIII was
established in 1986.
Although
clot formation is a normal
process, it sometimes occurs
inappropriately and
constitutes a threat to life.
In people who are hospitalized
for a long time, for example,
clots sometimes form in the
large veins of the legs (see
Thrombosis).
If these clots, or thrombi,
travel to the lungs, they can
cause death (see Embolism).
Such venous thrombi are
dissolved in many cases with a
combination of drugs that
prevent coagulation and break
down clots. Anticoagulants
include the natural compound
heparin, prepared from the
lungs and livers of animals,
and the synthetic chemicals
dicumarol and warfarin.
Clot-dissolving drugs, called
thrombolytics, include two
enzymes, urokinase and
streptokinase, approved for
medical use in 1979, and
tissue plasminogen activator
(TPA), a product of genetic
engineering.
Interaction
of thrombocytes with the fatty
deposits found in
atherosclerotic heart disease
is thought to contribute to
heart attacks. Compounds such
as aspirin and sulfinpyrazone,
which inhibit platelet
activity, may decrease heart
attacks in persons with
atherosclerotic disease.
Polio
Poliomyelitis ,
infectious virus disease of
the central nervous system,
sometimes resulting in
paralysis. The greatest
incidence of the disease, also
known as infantile paralysis,
is in children between the
ages of five and ten years.
The disease was described in
1840 by the German orthopedist
Jacob von Heine. In its
clinical form it is more
prevalent in temperate zones.
Symptoms
The virus
usually enters the body
through the alimentary tract
and spreads along nerve cells
to affect various parts of the
central nervous system. The
incubation period ranges from
about 4 to 35 days. Early
symptoms include fatigue,
headache, fever, vomiting,
constipation, stiffness of the
neck, or, less commonly,
diarrhea and pain in the
extremities. Because nerve
cells that control muscular
movement are not replaced once
they are destroyed, poliovirus
infection can cause permanent
paralysis. When nerve cells in
respiratory centers, which
control breathing, are
destroyed, the victim must be
kept alive by an iron lung (see
Artificial
Respiration).
For every paralytic case of
poliomyelitis, however, there
may be 100 nonparalytic cases.
Treatment
Because no
drug developed so far has
proved effective, treatment is
entirely symptomatic. The
Australian nurse Elizabeth
Kenny first initiated use of
moist heat coupled with
physical therapy to stimulate
the muscles, and antispasmodic
drugs are administered to
produce muscular relaxation.
In the convalescent stage, occupational
therapy
is used.
Disease
Control
Three broad
types of the virus have been
identified: the Brunhilde
(type 1), Lansing (type 2),
and Leon (type 3) strains.
Immunity to one strain does
not furnish protection against
the other two.
Poliomyelitis
control was made possible
when, in 1949, the American
bacteriologist John Franklin
Enders and his coworkers
discovered a method of growing
the viruses on tissue in the
laboratory. Applying this
technique, the American
physician and epidemiologist
Jonas Salk developed a vaccine
prepared from inactivated
poliomyelitis viruses of the
three known types. After field
trials in 1954 the vaccine was
pronounced safe and effective,
and mass inoculation began.
The American virologist Albert
Sabin subsequently developed a
vaccine containing attenuated,
live poliovirus that could be
given orally. This vaccine,
called trivalent oral polio
vaccine (TOPV), was licensed
in 1960 and has replaced the
Salk injectable vaccine as the
standard immunizing agent in
the United States. As a result
of routine immunization,
outbreaks of paralytic
poliomyelitis in the United
States declined dramatically
from 57,879 cases in 1952 to
only a few each year.
The
vulnerability of a population
that was not immunized was
demonstrated in 1979, when 16
cases of paralytic
poliomyelitis occurred among
Amish people in the United
States and Canada who had not
been vaccinated.
Measles
Measles,
also rubeola, acute, highly
contagious, fever-producing
disease caused by a filterable
virus,
different from the virus that
causes the less serious
disease German
measles,
or rubella. Measles is
characterized by small red
dots appearing on the surface
of the skin, irritation of the
eyes (especially on exposure
to light), coughing, and a
runny nose. About 12 days
after first exposure, the
fever, sneezing, and runny
nose appear. Coughing and
swelling of the neck glands
often follow. Four days later,
red spots appear on the face
or neck and then on the trunk
and limbs. In 2 or 3 days the
rash subsides and the fever
falls; some peeling of the
involved skin areas may take
place. Infection of the middle
ear may also occur.
Measles was
formerly one of the most
common childhood diseases.
Since the development of an
effective vaccine in 1963, it
has become much less frequent.
By 1988, annual measles cases
in the U.S. had been reduced
to fewer than 3500, compared
with about 500,000 per year in
the early 1960s. However, the
number of new cases jumped to
more than 18,000 in 1989 and
to nearly 28,000 in 1990. Most
of these cases occurred among
inner-city preschool children
and recent immigrants, but
adolescents and young adults,
who may have lost immunity (see
Immunization)
from their childhood
vaccinations, also experienced
an increase. In 1991, the
number of new cases dropped to
fewer than 10,000. The reasons
for this resurgence and
subsequent decline are not
clearly understood. In other
parts of the world measles is
still a common childhood
disease. In the U.S., measles
is rarely fatal; should the
virus spread to the brain,
however, it can cause death or
brain damage (see Encephalitis).
No specific
treatment for measles exists.
Patients are kept isolated
from other susceptible
individuals, usually resting
in bed, and are treated with
aspirin, cough syrup, and skin
lotions to lessen fever,
coughing, and itching. The
disease usually confers
immunity after one attack, and
an immune pregnant woman
passes the antibody in the
globulin fraction of the blood
serum, through the placenta,
to her fetus.
Germs
and Virus
Germs
Germ,
general term employed loosely
to designate any minute
pathogenic agent. The term is
applied to disease-producing
microorganisms, such as bacteria,
protozoa,
and fungi,
and to pathogenic agents of
uncertain classification,
such as rickettsia
and viruses (see Virus).
The term
germ became widely used after
the development of the germ
theory of disease in the 19th
century. Scientists and
science writers after the
beginning of the 20th century
have tended to use the
specific technical names of
particular microorganisms.
Virus
Virus (life
science),
infectious agent found in
virtually all life forms,
including humans, animals,
plants, fungi, and bacteria.
Viruses consist of genetic
material—either deoxyribonucleic
acid
(DNA) or ribonucleic
acid
(RNA)—surrounded by a
protective coating of protein,
called a capsid, with
or without an outer lipid
envelope. Viruses are between
20 and 100 times smaller than bacteria
and hence are too small to be
seen by light microscopy.
Viruses vary in size from the
largest poxviruses of about
450 nanometers (about 0.000014
in) in length to the smallest
polioviruses of about 30
nanometers (about 0.000001
in). Viruses are not
considered free-living, since
they cannot reproduce outside
of a living cell;
they have evolved to transmit
their genetic information from
one cell to another for the
purpose of replication.
Viruses
often damage or kill the cells
that they infect, causing disease
in infected organisms. A few
viruses stimulate cells to
grow uncontrollably and
produce cancers.
Although viruses cause many
infectious diseases, such as
the common cold,, there are no
cures for these illnesses. The
difficulty in developing
antiviral therapies stems from
the large number of variant
viruses that can cause the
same disease, as well as the
inability of drugs to disable
a virus without disabling
healthy cells. However, the
development of antiviral
agents is a major focus of
current research, and the
study of viruses has led to
many discoveries important to
human health.
Structure
and Classification
Individual
viruses, or virus particles,
also called virions,
contain genetic material, or genomes,
in one of several forms.
Unlike cellular organisms,
which have only DNA, viruses
have either DNA or RNA. Like
cell DNA, almost all viral DNA
is double-stranded, and it can
have either a circular or a
linear arrangement. Almost
all-viral RNA is
single-stranded; it is usually
linear, and it may be either
segmented (with different
genes on different RNA
molecules) or nonsegmented
(with all genes on a single
piece of RNA).
The viral
protective shell, or capsid,
can be either helical
(spiral-shaped) or icosahedral
(having 20 triangular sides).
Capsids are composed of
repeating units of one or a
few different proteins.
These units are called protomers
or capsomers. The
proteins that make up the
virus particle are called
structural proteins. Viruses
also carry genes for making
proteins that are never
incorporated into the virus
particle and are found only in
infected cells. These viral
proteins are called
nonstructural proteins; they
include factors required for
the replication of the viral
genome and the production of
the virus particle.
Capsids and
the genetic material (DNA or
RNA) they contain are together
referred to as nucleocapsids.
Some virus particles consist
only of nucleocapsids, while
others contain additional
structures.
Some
icosahedral and helical animal
viruses are enclosed in a
lipid envelope acquired when
the virus buds through
host-cell membranes.
Inserted into this envelope
are glycoproteins that
the viral genome directs the
cell to make; these molecules
bind virus particles to
susceptible host cells.
The most
elaborate viruses are the bacteriophages,
which use bacteria as their
hosts. Some bacteriophages
resemble an insect with an
icosahedral head attached to a
tubular sheath. From the base
of the sheath extend several
long tail fibers that help the
virus attach to the bacterium
and inject its DNA to be
replicated and to direct
capsid production and virus
particle assembly inside the
cell.
Disease-causing
agents that resemble
incomplete viruses are called viroids
and prions. Viroids are
plant pathogens that consist
only of a circular,
independently replicating RNA
molecule. The single-stranded
RNA circle collapses on itself
to form a rodlike structure.
The only known mammalian
pathogen that resembles plant
viroids is the deltavirus
(hepatitis D), which requires hepatitis
B virus proteins to package
its RNA into virus particles. Co-infection
with hepatitis B and D can
produce more severe disease
than can infection with
hepatitis B alone. Prions are
human and animal pathogens
that consist of only a protein
and lack nucleic acids. The
prion protein (PrP) can be
infectious and causes a fatal
neurological disease. A change
in the shape of PrP is
believed to be the key factor
in the development of the
disease.
Viruses are
classified according to their
type of genetic material,
their strategy of replication,
and their structure. The
International Committee on
Nomenclature of Viruses
(ICNV), established in 1966,
devised a scheme to group
viruses into families,
subfamilies, genera, and
species. The ICNV report
published in 1995 assigned
more than 4000 viruses into 71
virus families. Hundreds of
other viruses remain
unclassified because of the
lack of sufficient
information.
Replication
The first
contact between a virus
particle and its host cell
occurs when an outer viral
structure docks with a
specific molecule on the cell
surface. For example, a
glycoprotein called gp120 on
the surface of the human
immunodeficiency virus
(HIV, the cause of acquired
immune deficiency syndrome,
or AIDS) virion specifically
binds to the CD4 molecule
found on certain human T
lymphocytes (a type of white
blood cell). HIV cannot infect
most cells that do not have
surface CD4 molecules
generally.
After
binding to an appropriate
cell, a virus must cross the
cell membrane. Some viruses
accomplish this goal by fusing
their lipid envelope to the
cell membrane, thus releasing
the nucleocapsid into the
cytoplasm of the cell. Other
viruses must first be endocytosed
(enveloped by a small section
of the cell’s plasma
membrane that pokes into the
cell and pinches off to form a
bubblelike vesicle called an
endosome) before they can
cross the cell membrane.
Conditions in the endosome
allow many viruses to change
the shape of one or more of
their proteins. These changes
permit the virus either to
fuse with the endosomal
membrane or to lyse the
endosome (cause it to break
apart), allowing the
nucleocapsid to enter the cell
cytoplasm.
Once inside
the cell, the virus replicates
itself through a series of
events. Viral genes
direct the production of
proteins by the host cellular
machinery. The first viral
proteins synthesized by some
viruses are the enzymes
required to copy the viral
genome. Using a combination of
viral and cellular components,
the viral genome can be
replicated thousands of times.
Late in the replication cycle
for many viruses, proteins
that make up the capsid are
synthesized. These proteins
package the viral genetic
material to make newly formed
nucleocapsids.
To complete
the virus replication cycle,
viruses must exit the cell.
Some viruses bud out of the
cell’s plasma membrane by a
process resembling reverse
endocytosis. Other viruses
cause the cell to lyse,
thereby releasing newly formed
virus particles ready to
infect other cells. Still
other viruses pass directly
from one cell into an adjacent
cell without being exposed to
the extracellular environment.
The virus replication cycle
can be as short as a couple of
hours for certain small
viruses or as long as several
days for some large viruses.
Some
viruses kill cells by
inflicting severe damage
resulting in cell lysis; other
viruses cause the cell to kill
itself in response to virus
infection. This programmed
cell suicide is thought to be
a host defense mechanism to
eliminate infected cells
before the virus can complete
its replication cycle and
spread to other cells.
Alternatively, cells may
survive virus infection, and
the virus can persist for the
life of its host. Virtually
all people harbor harmless
viruses.
Retroviruses ,
such as HIV, have RNA that is
transcribed into DNA by the
viral enzyme reverse
transcriptase upon entry
into the cell. (The ability of
retroviruses to copy RNA into
DNA earned them their name
because this process is the
reverse of the usual transfer
of genetic information, from
DNA to RNA.) The DNA form of
the retrovirus genome is then
integrated into the cellular
DNA and is referred to as the provirus.
The viral genome is replicated
every time the host cell
replicates its DNA and is thus
passed on to daughter cells.
Hepatitis B
virus can also transcribe RNA
to DNA, but this virus
packages the DNA version of
its genome into virus
particles. Unlike
retroviruses, hepatitis B
virus does not integrate into
the host cell DNA.
Disease
Most viral
infections cause no symptoms
and do not result in disease.
For example, only a small
percentage of individuals who
become infected with
Epstein-Barr virus or western
equine encephalomyelitis virus
ever develop disease symptoms.
In contrast, most people who
are infected with measles,
rabies,
or influenza
viruses develop the disease. A
wide variety of viral and host
factors determine the outcome
of virus infections. A small
genetic variation can produce
a virus with increased
capacity to cause disease.
Such a virus is said to have
increased virulence.
Viruses can
enter the body by several
routes. Herpes
simplex virus and poxviruses
enter through the skin by
direct contact with
virus-containing skin lesions
on infected individuals. Ebola,
hepatitis B, and HIV can be
contracted from infected blood
products. Hypodermic needles
and animal and insect bites
can transmit a variety of
viruses through the skin.
Airborne droplets of mucus or
saliva from infected
individuals who cough or
sneeze usually transmit
viruses that infect through
the respiratory tract. Viruses
that enter through the
respiratory tract include
orthomyxovirus (influenza),
rhinovirus and adenovirus
(common cold), and
varicella-zoster virus (chicken
pox).
Viruses such as rotavirus,
coronavirus, poliovirus,
hepatitis A, and some
adenoviruses enter the host
through the gastrointestinal
tract. Sexually transmitted
viruses, such as herpes
simplex, HIV, and human
papilloma viruses
(HPV), gain entry through the
genitourinary route. Other
viruses, including some
adenoviruses, echoviruses,
Coxsackie viruses, and
herpesviruses, can infect
through the eye.
Virus
infections can be either
localized or systemic. The
path of virus spread through
the body in systemic
infections differs among
different viruses. Following
replication at the initial
site of entry, many viruses
are spread to their target
organs by the bloodstream or
the nervous system.
The
particular cell type can
influence the outcome of virus
infection. For example, herpes
simplex virus undergoes lytic
replication in skin cells
around the lips but can
establish a latent or dormant
state in neuron cell bodies
(located in ganglia) for
extended periods of time.
During latency, the viral
genome is largely dormant in
the cell nucleus until a
stimulus such as a sunburn
causes the reactivation of
latent herpesvirus, leading to
the lytic replication cycle.
Once reactivated, the virus
travels from the ganglia back
down the nerve to cause a cold
sore on the lip near the
original site of infection.
The herpesvirus genome does
not integrate into the host
cell genome.
Virus-induced
illnesses can be either acute,
in which the patient recovers
promptly, or chronic, in which
the virus remains with the
host or the damage caused by
the virus is irreparable. For
most acute viruses, the time
between infection and the
onset of disease can vary from
three days to three weeks. In
contrast, onset of AIDS
following infection with HIV
takes an average of 7 to 11
years.
Several
human viruses are likely to be
agents of cancer, which can
take decades to develop. The
precise role of these viruses
in human cancers is not well
understood, and genetic and
environmental factors are
likely to contribute to these
diseases. But because a number
of viruses have been shown to
cause tumors in animal models,
it is probable that many
viruses have a key role in
human cancers.
Some
viruses—alphaviruses and
flaviviruses, for example—must
be able to infect more than
one species to complete their
life cycles. Eastern equine
encephalomyelitis
virus, an alphavirus,
replicates in mosquitoes and
is transmitted to wild birds
when the mosquitoes feed.
Thus, wild birds and perhaps
mammals and reptiles serve as
the virus reservoir,
and mosquitoes serve as vectors
essential to the virus life
cycle by ensuring transmission
of the virus from one host to
another. Horses and people are
accidental hosts when an
infected mosquito bites them,
and they do not play an
important role in virus
transmission.
The most
common human prion disease is Creutzfeldt-Jakob
disease
(CJD), which has a worldwide
incidence of approximately one
in a million individuals and
is characterized by dementia.
Scrapie is the most common
prion disease in animals. Feed
for cattle generated from
scrapied sheep in Great
Britain has resulted in the
death of more than 150,000
cattle from bovine
spongiform encephalopathy,
or mad cow disease, since the
discovery of the disease in
1986. It is not yet known if
humans can develop CJD from
consuming prion-contaminated
beef, but several recent cases
in Great Britain suggest this
possibility.
Defense
Although
viruses cannot be treated with
antibiotics,
which are effective only
against bacteria, the body’s
immune
system
has many natural defenses
against virus infections.
Infected cells produce interferon’s
and other cytokines
(soluble components that are
largely responsible for
regulating the immune
response), which can signal
adjacent uninfected cells to
mount their defenses, enabling
uninfected cells to impair
virus replication. Some
cytokines can cause a fever in
response to viral infection;
elevated body temperature
retards the growth of some
types of viruses. B
lymphocytes produce specific
antibodies that can bind and
inactivate viruses. Cytotoxic
T cells recognize
virus-infected cells and
target them for destruction.
However, many viruses have
evolved ways to circumvent
some of these host defense
mechanisms.
The
development of antiviral
therapies has been thwarted by
the difficulty of generating
drugs that can distinguish
viral processes from cellular
processes. Therefore, most
treatments for viral diseases
simply alleviate symptoms,
such as fever,
dehydration, and achiness.
Nevertheless, antiviral drugs
for influenza virus,
herpesviruses, and HIV are
available, and many others are
in the experimental and
developmental stages.
Prevention
has been a more effective
method of controlling virus
infections. Viruses that are
transmitted by insects or
rodent excretions can be
controlled with pesticides.
Successful vaccines are
currently available for
poliovirus, influenza, rabies,
adenovirus, rubella, yellow
fever,
measles, mumps,
and chicken pox. Vaccines are
prepared from killed
(inactivated) virus, live
(attenuated or weakened)
virus, or isolated viral
proteins (subunits). Each of
these types of vaccines
elicits an immune response
while causing little or no
disease, and there are
advantages and disadvantages
to each. (For a more complete
discussion of vaccines, see
the Immunization
article.)
British
physician Edward Jenner
discovered the principle of
vaccination. In 1796 Jenner
observed that milkmaids in
England who contracted the
mild cowpox virus infection
from their cows were protected
from smallpox,
a frequently fatal disease. In
1798 Jenner formally
demonstrated that prior
infection with cowpox virus
protected those that he
inoculated with smallpox virus
(an experiment that would not
meet today’s protocol
standards because of its use
of human subjects). In 1966
the World Health Organization
(WHO) initiated a program to
eradicate smallpox from the
world. Because it was
impossible to vaccinate the
entire world population, the
eradication plan was to
identify cases of smallpox and
then vaccinate all of the
individuals in that vicinity.
The last reported case of
smallpox was in Somalia in
October 1977. An important
factor in the success of
eradicating smallpox was that
humans are the only host and
there are no animal reservoirs
for smallpox virus. The strain
of poxvirus used for
immunization against smallpox
was called vaccinia.
Introduction of the Salk
(inactivated) and Sabin (live,
attenuated) vaccines for
poliovirus, developed in the
1950s by the American
physician and epidemiologist Jonas
Salk
and the American virologist Albert
Bruce Sabin,
respectively, was responsible
for a significant worldwide
decline in paralytic
poliomyelitis. However, polio
has not been eradicated,
partly because the virus can
mutate and escape the host
immune response. Influenza
viruses mutate so rapidly that
new vaccines are developed for
distribution each year.
Viruses
undergo very high rates of
mutation (genetic alteration)
largely because they lack the
repair systems that cells have
to safeguard against
mutations. A high mutation
rate enables the virus to
continually adapt to new
intracellular environments and
to escape from the host immune
response. Co-infection of the
same cell with different
related viruses allows for
genetic reassortment (exchange
of genome segments) and
intramolecular recombination.
Genetic alterations can alter
virulence or allow viruses to
gain access to new cell types
or new animal hosts. Many
scientists believe that HIV is
derived from a closely related
monkey virus, SIV (simian
immunodeficiency virus), that
acquired the ability to infect
humans. Many of today’s
emerging viruses may have
similar histories.
Discovery
By the last
half of the 19th century, the
microbial world was known to
consist of protozoa,
fungi, and bacteria, all
visible with a light
microscope. In the 1840s, the
German scientist Jacob Henle
suggested that there were
infectious agents too small to
be seen with a light
microscope, but for the lack
of direct proof, his
hypothesis was not accepted.
Although the French scientist Louis
Pasteur
was working to develop a
vaccine for rabies in the
1880s, he did not understand
the concept of a virus.
During the
last half of the 19th century,
several key discoveries were
made that set the stage for
the discovery of viruses.
Pasteur is usually credited
for dispelling the notion of
spontaneous generation and
proving that organisms
reproduce new organisms. The
German scientist Robert
Koch,
a student of Jacob Henle, and
the British surgeon Joseph
Lister
developed techniques for
growing cultures of single
organisms that allowed the
assignment of specific
bacteria to specific diseases.
The German
scientist Adolf Mayer
accomplished the first
experimental transmission of a
viral infection in about 1880,
when he demonstrated that
extracts from infected tobacco
leaves could transfer tobacco
mosaic disease to a new plant,
causing spots on the leaves.
Because Mayer was unable to
isolate a bacterium or fungus
from the tobacco leaf
extracts, he considered the
idea that tobacco mosaic
disease might be caused by a
soluble agent, but he
concluded incorrectly that a
new type of bacteria was
likely to be the cause. The
Russian scientist Dimitri
Ivanofsky extended Mayer’s
observation and reported in
1892 that the tobacco mosaic
agent was small enough to pass
through a porcelain filter
known to block the passage of
bacteria. He too failed to
isolate bacteria or fungi from
the filtered material. But
Ivanofsky, like Mayer, was
bound by the dogma of his
times and concluded in 1903
that the filter might be
defective or that the disease
agent was a toxin
rather than a reproducing
organism.
Unaware of
Ivanofsky’s results, the
Dutch scientist Martinus
Beijerinck, who collaborated
with Mayer, repeated the
filter experiment but extended
this finding by demonstrating
that the filtered material was
not a toxin because it could
grow and reproduce in the
cells of the plant tissues. In
his 1898 publication,
Beijerinck referred to this
new disease agent as a
contagious living liquid—contagium
vivum fluid—initiating a
20-year controversy over
whether viruses were liquids
or particles.
The
conclusion that viruses are
particles came from several
important observations. In
1917 the French-Canadian
scientist Felix H. d’Hérelle
discovered that viruses of
bacteria, which he named
bacteriophage, could make
holes in a culture of
bacteria. Because each hole,
or plaque, developed from a
single bacteriophage, this
experiment provided the first
method for counting infectious
viruses (the plaque assay). In
1935 the American biochemist
Wendell Meredith Stanley
crystallized tobacco mosaic
virus to demonstrate that
viruses had regular shapes,
and in 1939 tobacco mosaic
virus was first visualized
using the electron microscope.
In 1898 the
German bacteriologists
Friedrich August Johannes Lِffler
and Paul F. Frosch (both
trained by Robert Koch)
described foot-and-mouth
disease
virus as the first filterable
agent of animals, and in 1900,
the American bacteriologist
Walter Reed and colleagues
recognized yellow fever virus
as the first human filterable
agent. For several decades
viruses were referred to as
filterable agents, and
gradually the term virus
(Latin for "slimy
liquid" or
"poison") was
employed strictly for this new
class of infectious agents.
Through the 1940s and 1950s
many critical discoveries were
made about viruses through the
study of bacteriophages
because of the ease with which
the bacteria they infect could
be grown in the laboratory.
Between 1948 and 1955,
scientists at the National
Institutes of Health (NIH) and
at Johns Hopkins Medical
Institutions revolutionized
the study of animal viruses by
developing cell culture
systems that permitted the
growth and study of many
animal viruses in laboratory
dishes.
Evolution
Three
theories have been put forth
to explain the origin of
viruses. One theory suggests
that viruses are derived from
more complex intracellular
parasites that have eliminated
all but the essential features
required for replication and
transmission. A more widely
accepted theory is that
viruses are derived from
normal cellular components
that gained the ability to
replicate autonomously. A
third possibility is that
viruses originated from
self-replicating RNA
molecules. This hypothesis is
supported by the observation
that RNA can code for proteins
as well as carry out enzymatic
functions. Thus, viroids may
resemble
"prehistoric"
viruses.
Importance
of Viruses
Because
viral processes so closely
resemble normal cellular
processes, abundant
information about cell biology
and genetics has come from
studying viruses. Basic
scientists and medical
researchers at university and
hospital laboratories are
working to understand viral
mechanisms of action and are
searching for new and better
ways to treat viral illnesses.
Many pharmaceutical
and biotechnology companies
are actively pursuing
effective antiviral therapies.
Viruses can also serve as
tools. Because they are
efficient factories for the
production of viral proteins,
viruses have been harnessed to
produce a wide variety of
proteins for industrial and
research purposes. A new area
of endeavor is the use of
viruses for gene therapy.
Because viruses are programmed
to carry genetic information
into cells, they have been
used to replace defective
cellular genes. Viruses are
also being altered by genetic
engineering
to kill selected cell
populations, such as tumor
cells. The use of genetically
engineered viruses for medical
intervention is a relatively
new field, and none of these
therapies is widely available.
However, this is a
fast-growing area of research,
and many clinical trials are
now in progress. The use of
genetically engineered viruses
extends beyond the medical
field. Recombinant insect
viruses have agricultural
applications and are currently
being tested in field trials
for their effectiveness as
pesticides. |
