Rabies virus is a bullet-shaped, single-stranded
negative-sense, enveloped RNA virus (denoted (-)ssRNA) and a member of the genus
Lyssavirus of the Rhabdoviridae family that
causes rabies (Figure 1). The virus has an average
diameter of 75 nm (nanometres) with lengths varying between
130 and 300 nm. Rabies virions contain four
major polypeptides of different molecular size.
One of them constitutes the protein moiety of
the viral nucleocapsid, which is a
single-stranded helical protein, whereas the
remaining three are considered to be components
of the viral envelope (Albertini et al.,
1997) (Figure 2).
It has been estimated that the envelope of a
rabies virion contains 1800 molecules of these
This transmission electron micrograph reveals the
bullet-shaped morphology of the rabies virus.
Nucleocapsid arrangement of the rabies virus
inferred from electron microscopy studies. The
coil represents the RNA genome.
Tightly encases genomic RNA.
P (not shown)
Associated with ribonucleoprotein core.
Associated both with envelope and
ribonucleoprotein core; may be central
protein of rhabdovirus assembly.
Forms roughly 400 trimeric spikes which
are tightly arranged on the viral
L (not shown)
Associated with the ribonucleoprotein
core, RNA-dependent RNA polymerase.
When a human is exposed to rabies
virus, the pathogen replicates at the site of
inoculation. Aided by the G protein, the viral
envelope attaches and fuses with the host cell
membrane. 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
ribonucleoprotein core into the
cytoplasm. Since the rabies virus has a linear
negative-sense RNA 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.
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.
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
ribonucleoprotein core.. The matrix
protein initiates coiling. After assembly, the
new complete virions bud off from the host cell,
and replication is complete.
The virus spreads between animals
through saliva secretions from an infected
animal, usually as a result of a bite that
breaks the skin. Once progeny virions are
released from the initial site of inoculation,
they migrate to the central nervous system via
the bloodstream where they subsequently infects
targeted cells. To date, the only cases of
human-to-human transmission were a result of
organ transplantations from undiagnosed patients
disease and the main hosts of the virus vary
depending on the geographic location. In the
vast majority of the developed world, carriers
of the virus are mostly wild carnivorous animals
like raccoons, foxes, and bats. However, in
areas such as Africa and China, dogs remain the
most significant carriers of the virus.
According to the World Health Organization,
55000 cases of rabies are reported annually with
95% of these cases occurring in Africa and
The incubation period of the virus is
approximately one to three months in 60% of
reported cases, but can last as little as 15
days to well over one year. The incubation
period of the virus allows it to migrate from
the point of entry (muscle tissue) to the
peripheral nervous tissue. From the peripheral
nervous system, the virus migrates to the
central nervous system by following the flow of
the axoplasm of neurons at an average rate of 8
to 20 mm per day (Takayama,
2008). The symptoms of rabies begin to appear
once the virus enters the central nervous
system. Within a period of twenty days after the
incubation period, the symptoms of the infection
progress from those that are nonspecific such as
fever and malaise to confusion, agitation,
hydrophobia and aerophobia. The patients finally
fall into comas and ultimately die from cardiac
arrest or respiratory failure (Fu, 1997). There
is currently no cure for rabies after the onset
of symptoms. It has been suggested that patients
succumb to the disease as a result of neuron
function alteration rather than tissue
destruction since many genes from recovered
tissues had decreased gene expression. Such
genes include nitric oxide synthase and
5-hydroxytryptamine receptors (Fu, 1997).
Diagnosis and Risk Factors: The
currently available methods for detecting viral
infections are unreliable, as they require the
rabies virus to be present in either saliva
samples or in a cerebrospinal fluid biopsy, at
which point it is too late to save the patient.
However, viral genes can be detected by reverse
transcriptase PCR or by detecting viral antigens
on skin samples using fluorescent antibodies (Takayama,
The virus is not
known to target specific demographics; all
mammals are at risk of contracting the virus.
However, most of the cases of rabies that are
reported occur in children that are between the
ages of 5 and 15; this can be due to lack of
education on the virus or a child’s naiveté.
Other people at risk are rural inhabitants or
people who have elevated contact time with
Albertini, A.A.V., Schoehn,
G., Weissenhorn, W. & Ruigrok, R.W.H. (2008).
Structural aspects of rabies virus replication.
Cellular and Molecular Life Sciences,
Fu, Z. F. (1997). Rabies and
rabies research: past, present and future.
Vaccine, 15: 20-24.
Takayawa, N. (2008). Rabies:
a preventable but incurable disease. Journal
of Infection and Chemotherapy, 14, 14: 8-14.