RABIES
Rabies is a viral disease that infects the central nervous system of
mammals, and death usually occurs within days of the onset of symptoms. Rabies is a rare disease in humans but has
been coined one of the most terrifying diseases known to man. (National Institute of Allergy and Infectious Diseases) About 18,000 Americans receive rabies shots
yearly due to contact with rabid animals.
During the past century, rabies has changed dramatically.
Figure 1.
Animal Rabies Cases (CDC).
Though the majority of cases before 1960 were in domestic animals, 90%
of cases reported annually to the CDC occur in wild animals like raccoons,
skunks, bats, and foxes. (CDC)
Transmission of the virus usually begins when an uninfected animal comes
in contact with the saliva of an infected host. Other routes of transmission include corneal transplantations,
contamination of mucous membranes, and aerosol transmission.
Rabies
Virus
The rabies virus is classified in the Rhabdoviridae family of the
Mononegavirale order of viruses.
It is further divided into the Lyssavirus genus, which includes the rabies virus, Lagos bat, Mokola virus,
Duvenhage virus, European bat virus 1 & 2 and Australian bat virus. The rabies virus structure involves a bullet-shaped
particle composed of a non-segmented, linear, negative sense single-stranded
piece of RNA (-ssRNA). (CDC)
Two major structural components shared by all rhabdovirus include a
helical ribonucleoprotein core (RNP) and a surrounding envelope (Figure
2). In particular, the rabies virus
also encodes for the following five proteins:
|
Protein |
Symbol |
Function |
|
nucleoprotein |
N |
tightly encases genomic RNA |
|
phosphoprotein |
P |
associated with RNP |
|
matrix protein |
M |
associated both with envelope and RNP;
may be central protein of rhabdovirus assembly |
|
glycoprotein |
G |
forms ~400 trimeric spikes which are
tightly arranged on the viral surface |
|
polymerase |
L |
associated with the RNP, RNA dependent
RNA polymerase |
These proteins are located on the rabies genome as
depicted in Figure 3. In addition, the
virulence factors for the rabies virus include the G protein, glycoprotein, and
cytopathic effects associated with the disease.
Viral Replication Process
When a human or animal is injected with infected
saliva, the rabies virus replicates at the site of inoculation. Aided by the G protein, the viral envelope
attaches and fuses with the host cell membrane (Figure 4, part 2). Invagination of the plasma membrane with
clathrin-coated pits allows cytoplasmic absorption via pinocytosis. The virions aggregate with the large
endosomes, and after fusion with their membranes, they initiate the uncoating
and release of the viral RNP into the cytoplasm (Figure 4, part 3). Since the rabies virus has a linear –ssRNA
genome, messenger RNAs are produced to permit virus replication using the host
cell machinery. In particular,
translation of the genome occurs on the free ribosomes in the cytoplasm, and
some posttranslational processing occurs in the endoplasmic reticulum and Golgi
apparatus.
Figure 4.
Rabies virus cycle of infection and replication (CDC)
The switch from transcription to replication is
triggered by the ratio of leader RNA to N protein and this subsequently causes
replication of positive RNA strands of the viral genome. (CDC)
Translation of the rabies genome then occurs, sequentially producing the
N, P, M, G, and L protein components.
Full-length copies of the positive strands become templates for the new
viral negative-stranded RNA. As the
virion is assembled in the host cell, the newly synthesized RNA is complexed
with the N, P, and L proteins to create the RNP core. The matrix protein initiates coiling. After assembly, the new complete virions bud off from the host
cell, and replication is complete.
Transmission
Transmission of the virus usually begins when an uninfected animal comes
in contact with the saliva of an infected host. Other routes of transmission include contamination of mucous
membranes and aerosol transmission, often in caves inhabited by bats. Another rare occurrence of rabies
transmission occurred via a corneal transplant to a patient in France. (UF College of Medicine)
Figure 5.
Rabies Reservoirs in the United States (CDC).
All warm-blooded mammals are at-risk for contracting rabies and for
serving as natural reservoirs of the virus.
Symptoms and Diagnosis
|
Animals |
Humans |
|
- may appear sick, crazed, or vicious (“mad dog”) - may also appear overly friendly, docile, or confused - nocturnal animals alert during the day |
- pain, tingling, and/or itching at bite site. - nonspecific – fever, chills, fatigue, muscle aches - later – high fever, agitation, confusion - extreme hydrophobia and aerophobia |
|
|
- death during later stages |
|
|
When the virus first enters the body via an infected bite, it first
spreads from the inoculum region to the spinal cord and onto the brain. After replication in the brain, the virus
travels outward to many locations of the body, including the salivary glands
and corneal epithelial cells. The most
interesting characteristic of the rabies virus is that it infects the brain,
causing the animal to want to bite, and then concentrates itself in the
salivary glands to ensure transmission its next host. (UF College of Medicine)
The dFA (direct fluorescent antibody test) is the standard diagostic
method in detecting the rabies virus. All
laboratories in the United States perform this test post-morteum for any animal
suspected of rabies. Since the rabies
virus is present in infected nervous tissue, the test focuses on brain and
spinal cord samples to search for the presence of rabies virus proteins
(antigen). Infected tissues appear
green-yellow under a fluorescence microscope.
(CDC)
Histopathology is another available method but is not considered
appropriate for diagnostic measures.
At the Centers for Disease Control, surveillance of the rabies virus is
collected from human and animal cases and reported in annual summaries.
Figure 6.
United States Rabies Cases (CDC)
Figure 6 examines the prevalence of reported cases in the United
States. Most cases involve raccoons,
coyotes, and bats.
Treatment and Prevention
Once symptoms for rabies appear, there is no treatment. However, a vaccine can be administered after
an exposure (postexposure prophylaxis) to provide immunity. In addition, some at-risk individuals who
may come in contact with rabies often (veterinarians, laboratory works,
international travelers) may receive a vaccine before exposure. This method of prevention is monitored every
few months for antibodies in the blood, and ultimately simplifies therapy by
decreasing the number of vaccine doses needed and eliminating the use of human
rabies immune globulin. If a person
becomes infected with rabies, he or she would receive a course of rabies immune
globulin and five doses of vaccine.
Over a four-week period, this treatment typically exceeds $1,000. (CDC)
References
eMedicine Consumer Health, 2003. http://emedicinehealth.com/articles/13096-3.asp?pd=2/4/2004+9%3A32%3A15+AM
National Institute of
Allergy and Infectious Diseases, National Institutes of Health, U.S. Department
of Health and Human Services. April 2002. http://www.niaid.nih.gov/factsheets/rabies.htm
National Center for
Infectious Diseases, Center for Disease Control and Prevention, Rabies website.
December 2003. http://www.cdc.gov/ncidod/dvrd/rabies/introduction/intro.htm
Rabies Lab, Kansas
State University, College of Veterinary Medicine. October 2003. http://www.vet.ksu.edu/depts/rabies/links.htm
University
of Florida, College of Medicine. May 1999. http://www.medinfo.ufl.edu/year2/mmid/bms5300/bugs/rabies.html