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Rabies: How It Works
Anthony Wong
Cluster 7
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The human body is like a door, mostly impenetrable, generally protected. And like most
doors, the human body can be opened by specific keys. Some of these keys are held by a trusted
neighbor or the local housekeeper. But others are held by burglars, by the thieves, and these
individuals get through the body’s door with the specific intent of wreaking as much havoc as
they can in the human body. Immunologists have given these certain individuals a name:
viruses. And rabies is one of those viruses, evolved to infiltrate the body and turn it into a
whirlpool of insane self-destruction.
Rabies is a variation of lyssaviruses, which are members of the family Rhabdoviridae.
This family’s name is derived from the Greek term rhabdos, meaning rods, which describes the
bullet-like structure of the viruses within the family. According to the National Center for
Biotechnology Information (NCIB), “The family Rhabdoviridae consists of more than one
hundred single-stranded, negative-sense, non-segmented viruses that infect a wide variety of
hosts, including vertebrates, invertebrates, and plants.” (par. 10) However, rabies is the most
prevalent in the immunology canon of Rhabdoviridae. Unlike its relatives, rabies is one of the
few viruses that is singularly transmitted by the saliva (and therefore the bite) of a warm-blooded
animal, and is even more unique in its infection and dissemination in the body. Additionally,
rabies targets the brain, using the peripheral nervous system to springboard the infection to affect
other organs and the rest of the body.
The peripheral nervous system is the section of the nervous system that is not protected
by the skull or spinal cord, making it particularly vulnerable to infection and toxin exposure. It
consists of the external ganglia and the nerves that are spread out throughout the body, and
connected directly to the brain. Rabies does not always primarily target the peripheral nervous
system; other cases have shown the virus to sometimes replicate itself in muscle tissue during the
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incubation period (one week – three months). It is also not entirely known which organs rabies
goes for first during the incubation period, as each case has revealed multiple antigens in
different organs. However, the virus always targets the salivary glands, the effects of which can
be seen in the extreme salivation and drool of rabies victims. In addition, the rabies virus also
always makes its way into the brain, explaining the increased aggression and salivation,
confusion, hydrophobia, and aerophobia that is so commonly observed in rabies victims. Closer
examinations of the brain have also shown mild clogging of meningeal vessels, tissue
degradation, neural cell compression, and in some cases, neuronophagia (phagocytosis of brain
cells).
Though the time frame of a rabies infection (from inoculation to death) can vary
from case to case, there are generally three stages of infection that develop in most mammals.
After the incubation period, there is the first stage, or prodromal stage, where the victim will
experience behavioral changes. The second stage, or “furious” stage, is the most notorious
indication of rabies, and is where the victim becomes noticeably more aggressive. The third
stage, which can vary from case to case, can have the victim experiencing the “paralysis” stage,
or a comatose state that quickly leads to death. All fatalities from rabies are caused by
respiratory and/or cardiac arrest, and only accompanied by various levels of brain entropy.
However, to fully map the process of rabies pathogenesis, we have to understand the
virus’s physical structure. Rabies is an RNA virus, meaning that rabies uses RNA to store
genetic material. This characteristic contributes to the fact that RNA viruses are generally very
hard to develop vaccines for, due to their high mutation rates.
But by isolating the proteins
responsible for infection, immunologists can develop a suitable version of the virus that can be
used in vaccinations.
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Rhabdoviruses, on the whole, are composed of two main structures: a helical
ribonucleoprotein center (RNP), and an encapsulating membrane. The proteins produced by the
rabies genome are: nucleoprotein (N), phosphoprotein (P), maxtrix protein (M), glycoprotein
(G), and polymerase (L). Each protein plays a role in inoculation, infection, and propagation.
After inoculation, rabies immediately begins to spread, using its (G) protein to interact
with certain surface receptors on a host’s cell. This allows the virus to completely envelop the
cell, and insert itself into the cell through pintocytosis. Once rabies is within the cell, it releases
viral RNP into the cytoplasm and starts to replicate. Since rabies is an RNA virus, it requires
mRNA to transcribe in order to initiate the replication process.
Rabies then uses its (L) gene to transcribe the rabies RNA into the cell’s RNA, thereby
hijacking the cell’s protein manufacturing process. By blending all its proteins into various
ribosomes throughout the cell, rabies forces the now infected cell to make copies of its viral
proteins. Though individual ribosomes do most of the hard work of making new rabies proteins,
transcription also takes place in the cell’s endoplasmic reticulum and the golgi apparatus. Once
this process starts, it is very hard to stop. The rabies virus employs its (N) protein to take charge
of the metaphorical switch controlling production of the rogue proteins. And by “take charge of
the switch”, it means that the (N) protein pretty much shuts it off. This induces an overdrive
effect in the protein manufacturing process of the cell, making the cell churn out massive
amounts of the rabies proteins. To further accelerate the production, synthesized positive strands
of rabies genome are used as templates to create the negative strands. As the replication
continues, the quantity of the rabies genomes puts pressure on the membranes of the host cell,
eventually rupturing the cell and sending the finished copies of the rabies virus into the
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bloodstream, where it can go infect other cells, and begin the whole process of infection and
replication all over again.
Barring external treatment after infection, the victim may have some innate defenses
against the rabies virus. However, this response depends on the specific animal species; the type
of the rabies virus; concentration of the virus; and the location of viral inoculation. If the victim
received rabies vaccination prior to infection, the formulation of cytokines, such as interferon,
can halt the spread of the infection and eradicate the virus from the host system. However, this
positive resistance can only be achieved if the vaccine is given before the victim contracts rabies,
or shortly after inoculation. The NCIB has also noted that, “In one clinical trial…all subjects
died despite experimental treatment with high doses of alpha interferon.” (par. 23) It is possible
that the time between infection and administration of the alpha interferon was too long for the
dosage to have any effect. It should be noted that in the most effective recovery methods for the
rabies virus, diagnostic speed and quick vaccination is vital to the victim’s survival.
To prevent the contraction of rabies, the World Health Organization and the Center for
Disease Control (CDC) suggest obtaining vaccines at birth, a fact that has prompted many
health-care providers to prescribe the rabies vaccine to infants. In terms of active prevention, the
CDC recommends keeping pet immunization records up-to-date; keeping pets under control;
reporting suspicious behavior in wild animals to community animal control; and avoiding contact
with wild animals or strays altogether. And though traditional wildlife (i.e. raccoons, possums,
squirrels, and rabbits) are mostly publicized to be the main transmitters of rabies, the CDC noted
that “…from 1985 through 1994, woodchucks accounted for 86% of the 368 cases of rabies
among rodents reported to the CDC…”, and that “…Woodchucks or groundhogs (Marmota
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monax) are the only rodents that may be frequently submitted to state health department because
of a suspicion of rabies.”
If bitten by a potentially rabid animal, one must wash the wound as quickly as possible
for ten to fifteen minutes, as well as contact their nearest health provider and determine whether
a post-inoculation of the vaccine is necessary.
The U.S. has also mandated the maintenance of local rabies infection surveillance. In
each state, state administrations monitor and submit surveillance data to the CDC annually, and
are advertised to be the best source of information on rabies in an individual’s community. The
CDC also publishes its annual reports on its website, citing individual state information in a
synthesized manuscript. This summary discusses reported cases of rabies in wild and domestic
animals; viral distribution patterns; and various maps showing certain areas of high rabies
concentration.
The main characteristic of rabies that sets it apart from most viruses is its ability to
penetrate the nervous system, a part of the body that is generally closed off to most foreign
bodies. From there, rabies takes control of the body’s cells through the use of its (N), (P), (M),
(G), (L) proteins, dividing and spreading until nearly all sane, cognitive function of the brain is
wiped out. To many countries around the world with no access to the vaccine, rabies is the very
personification of death.
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Works Cited
Chang, Wei-li. Stanford University: Rhabdoviridae. Stanford University, Mar. 2004. Web. 19
July 2015. <http://web.stanford.edu/group/virus/rhabdo/2004bischoffchang/Rhabdo.htm>.
N/A. "Characteristics of Rabies." Characteristics of Rabies. N/A, n.d. Web. 17 July 2015.
<http://homepage.usask.ca/~vim458/virology/studpages2007/Ann_Leighton/characteristicsofrabi
es.html>.
N/A. "Characteristics of Rabies." Characteristics of Rabies. N/A, n.d. Web. 17 July 2015.
<http://homepage.usask.ca/~vim458/virology/studpages2007/Ann_Leighton/characteristicsofrabi
es.html>.
N/A. "Rabies." CDC: Rabies. Center for Disease Control and Prevention, n.d. Web. 12 July
2015. <http://www.cdc.gov/rabies/>.
N/A. "Rabies." Rabies. Wikipedia, n.d. Web. 12 July 2015.
<https://en.wikipedia.org/wiki/Rabies>.
N/A. "The Rabies Virus." CDC: The Rabies Virus. Center for Disease Control and Prevention,
n.d. Web. 17 July 2015. <http://www.cdc.gov/rabies/transmission/virus.html>.
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N/A. "What Are the Parts of the Nervous System." NICHD: Parts of the Nervous System.
National Institute of Health and Human Development, n.d. Web. 19 July 2015.
<http://www.nichd.nih.gov/health/topics/neuro/conditioninfo/Pages/parts.aspx>.
Rupprecht, Charles E., PhD. "Rhabdoviruses: Rabies Virus." Medical Microbiology. 4th ed.
Galveston: University of Texas Medical Branch, 1996. N/A. Medical Microbiology. National
Center for Biotechnology Information. Web. 12 July 2015.
<http://www.ncbi.nlm.nih.gov/books/NBK8618/>.