ANATOMY AND PHYSIOLOGY of Rabies

Figure 1: This figure shows the bullet-shaped structure of

the Rabies Virus.
It is believed that the reaction of theG protein to the
cell surface receptors may be involved. After this occurs,
the virus goes through the host cell and enters the
cytoplasm by pinocytosis (which can be seen in Figure 2).

Figure 2: This figure shows the process of pinocytosis,

which allows the virus to enter the cytoplasm.
The virus cumulates in large endosomes and the endosome
membranes fuse together with the viral membranes, which
causes the release of viral RNP into the cytoplasm. The L
gene transcribes the rabies RNA into leader RNA and mRNAs,
which are then translated into proteins. The intracellular
ratio of leader RNA to the N protein stimulates the switch
from transcription to replication. After replication is
complete, the assembly process begins. The N-P-L complex
surrounds negative-stranded RNA to form the RNP core. The M
protein forms a capsule around the RNP. This RNP-M complex
travels to a part of the plasma membrane containing
glycoprotein inserts. Here, the M protein initiates
coiling. The RNP-M binds to the glycoprotein and the
completed virus buds from the plasma membrane. In the
central nervous system, there occurs preferential viral
budding from the plasma membrane. However, the virus in the
salivary glands mostly buds from the cell membranes into
the acinar lumen. This viral budding in the salivary
glands, as well as the aggressive biting behavior of the
infected animal, increases the chance of a viral infection
of a new host.

Figure 3: This figure shows the cycle of rabies infection

and replication.
Rabies is zoonotic, meaning that it is transferred by
animals, most commonly by the bite of a rabid animal.
However, it can be transferred in other manners. All warmblooded animals are susceptible to getting rabies. It
usually has an incubation period of between 2-12 weeks, but
there have been documented cases of incubation lasting up
to a year. The onset of symptoms is determined by the bites
proximity to the brain and the number of virus particles in
the infection. Negri bodies, which are characteristic of
rabies, are inclusion bodies that are commonly found in the
cytoplasm of infected nerve cells.
Figure 4: This figure shows Negri bodies located in a
rabies-infected nerve cell.
The virus is located in the nerves as well as the saliva of
an infected and symptomatic individual, however
transmission between humans is rare. After a human is
bitten, the virus enters the peripheral nervous system. The
virus binds to the nerves via nicotinic acetylcholine

receptors. During this time after a person is first

infected, rabies is hard to detect and does not present
symptoms. This is the time when a person can receive
vaccination. Once the virus reaches the brain, it quickly
causes encephalitis, or inflammation of the brain. The
cells in the brain that are affected include the
cerebellum, the purkinje cells, the hippocampus, and the
pontine nuclei. This stage of rabies is referred to as the
prodromal phase and is the onset of symptoms. Once the
virus moves along the nerve axons from the peripheral
nerves to the central nervous system (through retrograde
axoplasmic flow), the patient starts exhibiting symptoms.
It is believed that the neuromuscular junctions are very
important during this transition, as their physical and
chemical properties appear to direct the virus to infect
the nerve cells, (Hunt, 2009). This usually occurs through
the sensory and motor nerves. Treatment becomes
ineffective at this point and the mortality rate is almost
100%.
Once the virus reaches the central nervous system the virus
amplifies very quickly because of multiple cycles of
replication. This stage of rabies is known as the acute
neurological period. The centrifugal spread of rabies leads
to the virus overtaking very innervated areas, such as the
salivary glands. Once there is cerebral infection,
behavioral symptoms occur. The first symptoms to occur are
usually numbness and pain where bitten. Other early
symptoms include fever, cough, sore throat, abdominal pain,
and anxiety. Later symptoms that effect the central nervous
system are more pronounced and include anxiety,
hallucinations, delirium, hydrophobia, muscle spasms in the
face, neck, and diaphragm followed by seizures, paralysis,
significant fluctuations in temperature, heart rate and
blood pressure, coma, and heart and respiratory failure.
Hallucinations and delirium are the result of brain
inflammation and other dysfunctions occurring in the brain
such as dopamine. Encephalitis is also known to cause
seizures because the neurons firing in a patients brain
with encephalitis misfire, causing the seizure. Paralysis
occurs because of the damage being done to the nervous
system. Death usually occurs between three and twenty days
after the onset of symptoms. The virus is concentrated in
the salivary glands, which explains why it is transferred
usually by bites. The virus also damages the muscles
involved in swallowing (usually paralyzing them), which
causes a lot of pain. Because swallowing causes so much
pain, the patient usually becomes dehydrated, and thus,
very afraid of water. This is why the disease was once
called hydrophobia. Dehydration causes the muscle spasms
that patients can have. There are two main ways in which

these symptoms present themselves. The more common type is

known as furious rabies. This type includes seizures,
periods of anxiety, hallucinations, and violent behavior.
The second form is known as paralytic rabies. This is
characterized by a slow paralysis of the patient and
typically these patients live a little longer than those
who have furious rabies. The result of death is usually
respiratory failure.
Figure 5: This figure shows the progression of rabies from
transmission onward.
There are two different types of rabies prophylaxis that
are effective when used before the onset of symptoms. The
first, Rabies Vaccine, is an inactivated vaccine and is
immunogenic. It is grown in human diploid cells and is
given by injection over a four-week period. Human Rabies
Immunoglobin (HRIG), another treatment for rabies, is made
from the plasma of hyperimmune donors. About half of the
dose is injected into the site of the bite and the other
half is given through intramuscular injections. There two
treatments are used in conjunction with one another. These
treatments should be administered no later than 2 days
after the bite occurs.
It is still unknown what occurs during the long incubation
period of the disease and the molecular mechanism in which
the virus attacks the nervous system. However, there has
been a lot of progress with the control of rabies and the
development of vaccinations. Overall, rabies is a
frightening disease and hopefully one day scientists will
be able to eliminate, or at least reduce its incidence rate
significantly.
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