Rabies virus, Vaccine , treatment etc

1. Rabies virus
The rabies virus is a neurotropic virus that causes rabies in humans and animals. Rabies
transmission can occur through the saliva of animals and less commonly through contact with
human saliva.
Rabiesis a deadly virus that attacks the CNS (central nervous system) and causes acuteencephalitis.
The rabies virus has a cylindrical morphology and is the type species of the Lyssavirus genus of
theRhabdoviridae family. These viruses are enveloped and have a single stranded RNA genome
withnegative-sense. The genetic information is packaged as a ribonucleoprotein complex in
which RNA is tightly bound by the viral nucleoprotein.
The RNA genome of the virus encodes five genes whose order is highly conserved. These genes
code for nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and the
viral RNA polymerase (L).The complete genome sequences range from 11,615 to 11,966 nt in
length.
All transcription and replication events take place in the cytoplasm inside a specialized “virus
factory”, the Negri body (named after Adelchi Negri. These are 2–10 µm in diameter and are
typical for a rabies infection and thus have been used as definite histological proof of such
infection .
Virus classification
Group: Group V ((-)ssRNA)
Order: Mononegavirales
Family: Rhabdoviridae
Genus: Lyssavirus
Species: Rabies virus

2. Structure:
Lyssaviruses have helical symmetry, so their infectious particles are approximately cylindrical in
shape. They are characterized by an extremely broad host spectrum ranging from plants to
insects and mammals; human-infecting viruses more commonly have icosahedral symmetry
and take shapes approximating regular polyhedra.
The rabies virus has a bullet like shape with a length of about 180 nm and a cross-sectional
diameter of about 75 nm. One end is rounded or conical and the other end is planar or concave.
The lipoprotein envelope carries knob-like spikes composed of Glycoprotein G. Spikes do not
cover the planar end of the virion (virus particle). Beneath the envelope is the membrane or
matrix (M) protein layer which may be invaginatedat the planar end. The core of the virion
consists of helically arranged ribonucleoprotein.
Life cycle
After receptor binding, rabies virus enters its host cells through the endosomal transport
pathway. Inside the endosome, the low pH value induces the membrane fusion process, thus
enabling the viral genome to reach the cytosol. Both processes, receptor binding and
membrane fusion, are catalyzed by the glycoprotein G which plays a critical role in
pathogenesis (mutant virus without G proteins cannot propagate).
The next step after entry is the transcription of the viral genome by the P-L polymerase (P is an
essential cofactor for the L polymerase) in order to make new viral protein. The viral
polymerase can only recognizeribonucleoprotein and cannot use free RNA as template.
Transcription is regulated by cis-acting sequenceson the virus genome and by protein M which
is not only essential for virus budding but also regulates the fraction of mRNA production to
replication. Later in infection, the activity of the polymerase switches to replication in order to
produce full-length positive-strand RNA copies. These complementary RNAs are used as
templates to make new negative-strand RNA genomes. They are packaged together with
protein N to form ribonucleoprotein which then can form new viruses.
Infection
In September 1931, Joseph Lennox Pawan of Trinidad in the West Indies, a Government
Bacteriologist, found Negri bodies in the brain of a bat with unusual habits. In 1932, Pawan first
discovered that infected vampire bats could transmit rabies to humans and other animals. For a

3. brief history of some of the controversies surrounding the early discoveries relating to rabies in
Trinidad, see the brief history by James Waterman.
From the wound of entry, the rabies virus travels quickly along the neural pathways of
the peripheral nervous system. The retrograde axonal transport of the rabies virus to the CNS
(Central Nervous System) is the key step of pathogenesis during natural infection. The exact
molecular mechanism of this transport is unknown although binding of the P protein from
rabies virus to the dynein light chain protein DYNLL1 has been shown. P also acts as
an interferon antagonist, thus decreasing the immune response of the host.
From the CNS, the virus further spreads to other organs. The salivary glands located in the
tissues of the mouth and cheeks receive high concentrations of the virus, thus allowing it to be
further transmitted due to projectile salivation.
Fatality can occur from two days to five years from the time of initial infection. This however
depends largely on the species of animal acting as a reservoir. Most infected mammals die
within weeks, while strains of a species such as the African Yellow Mongoose (Cynictis
penicillata) might survive an infection asymptomatically for years.
Antigenicity
Upon viral entry into the body and also after vaccination, the body produces virus neutralizing
antibodies which bind and inactivate the virus. Specific regions of the G protein have been
shown to be most antigenic in leading to the production of virus neutralizing antibodies. These
antigenic sites, or epitopes, are categorized into regions I-IV and minor site a.
Previous work has demonstrated that antigenic sites II and III are most commonly targeted by
natural neutralizing antibodies. Additionally, a monoclonal antibody with neutralizing
functionality has been demonstrated to target antigenic site I. Other proteins, such as the
nucleoprotein, have been shown to be unable to elicit production of virus neutralizing
antibodies. The epitopes which bind neutralizing antibodies are both linear and conformational.
Transmission
All warm-blooded species, including humans, may become infected with the rabies virus and
develop symptoms. Birds were first artificially infected with rabies in 1884; however, infected
birds are largely if not wholly asymptomatic, and recover. Other bird species have been known
to develop rabies antibodies, a sign of infection, after feeding on rabies-infected mammals.
Rabies may also spread through exposure to infected domestic farm
animals, groundhogs, weasels, bears, and other wild carnivorans. Smallrodents, such

4. as squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, and mice, and lagomorphs such
as rabbits and hares, are almost never found to be infected with rabies and are not known to
transmit rabies to humans. Bites from mice, rats, or squirrels rarely require rabies prevention
because these rodents are typically killed by any encounter with a larger, rabid animal, and
would, therefore, not be carriers. The Virginia opossum is resistant but not immune to rabies.
The virus is usually present in the nerves and saliva of a symptomatic rabid animal. The route
of infection is usually, but not always, by a bite. In many cases, the infected animal is
exceptionally aggressive, may attack without provocation, and exhibits otherwise
uncharacteristic behavior. This is an example of a viral pathogen modifying the behavior of its
host to facilitate its transmission to other hosts.
Evolution
All extant rabies viruses appear to have evolved within the last 1500 years. There are seven
genotypes of rabies virus. In Eurasia cases are due to three of these—genotype 1 (classical
rabies) and to a lesser extent genotypes 5 and 6 (European bat lyssaviruses type-1 and -2).
Genotype 1 evolved in Europe in the 17th century and spread to Asia, Africa and the Americas
as a result of European exploration and colonization.
Bat rabies in North America appears to have been present since 1281 CE (95% confidence
interval: 906–1577 CE).
Rabies vaccine
A rabies vaccine is a vaccine used to prevent rabies.[1] There are a number of available vaccines
that are both safe and effective. They can be used to prevent rabies before and for a period of
time after exposure to the virus such as by a dog or bat bite. The immunity that develops is long
lasting after three doses. They are usually given by injection into the skin or muscle.
After exposure vaccination is typically used along with rabies immunoglobulin. It is
recommended that those who are at high risk of exposure be vaccinated before potential
exposure. Vaccines are effective in humans and other animals. Immunizing dogs is very
effective in preventing human disease.
They may be safely used in all age groups. About 35 to 45 percent of people develop a brief
period of redness and pain at the injection site. About 5 to 15 percent of people may
have fever,headaches or nausea. After exposure to rabies there is no contraindication to its
use. Most vaccines do not contain thimerosal.

5. Vaccines made from nerve tissue, and relied upon by a few countries, mainly in Asia and Latin
America, are less effective and have greater side effects.Their use is thus not recommended by
the World Health Organization.
Millions of people globally have been vaccinated and it is estimated that this saves more than
250,000 people a year.]It is on the World Health Organization's List of Essential Medicines, the
most important medication recommended for a basic health system.
Duck embryo vaccine
Purified Duck embryo vaccine (PDEV) was the first vaccine developed for human use in treating
pre- and postexposure to the rabies virus. It was developed in 1957 and was made of dried,
killed rabies virus. Vaccination with DEV involved a series of intradermal injections over several
days.
The World Health Organization still includes DEV in its list of recommended vaccines for
treatment of rabies virus exposure. However, newer vaccines are more commonly used. These
include the human diploid cell vaccine (HDCV) first introduced in 1978; purified chicken embyro
cell vaccine (PCECV), developed in 1984; and a purified Vero cell rabies vaccine (PVCRV)
developed in 1986.
 Application
Rabies virus is used in research for viral neuronal tracing to establish synaptic connections and
directionality of synaptic transmission.
 References
1. "Rabies Fact Sheet N°99". World Health Organization. July2013. Retrieved 28 February2014.
2. ^ Jump up to:a b c
Cotran RS, Kumar V, Fausto N (2005). Robbinsand Cotran Pathologic Basisof Disease (7th ed.).
Elsevier/Saunders. p. 1375.ISBN 0-7216-0187-1.
3. Jump up^"Rabies, Australian bat lyssavirus and other lyssaviruses". The Department of Health. Dec 2013. Retrieved 1
March 2014.
4. ^ Jump up to:a b c
Tintinalli, Judith E. (2010). EmergencyMedicine: A Comprehensive StudyGuide (EmergencyMedicine
(Tintinalli)). McGraw-Hill. pp. Chapter 152. ISBN 0-07-148480-9.
5. Jump up^William H. Wunner (2010). Rabies: Scientific Basis of the Disease and Its Management. Academic Press.
p. 556. ISBN 9780080550091.
6. Jump up^Hemachudha T, Ugolini G, Wacharapluesadee S, Sungkarat W, Shuangshoti S, Laothamatas J (May2013).
"Human rabies: neuropathogenesis, diagnosis, and management.". Lancet neurology 12(5): 498–
513. doi:10.1016/s1474-4422(13)70038-3.PMID 23602163.