Rabies virus (Lyssavirus rabies) is a neurotropic virus that causes rabies in animals, including humans. It can cause violence, hydrophobia, and fever. Rabies transmission often occurs through the saliva of animals and less commonly through contact with human saliva. Rabies virus, like many rhabdoviruses, has an extremely wide host range. In the wild it has been found infecting many mammalian species, while in the laboratory it has been found that birds can be infected, as well as cell cultures from mammals, birds, reptiles and insects. Rabies is reported in more than 150 countries and on all continents except Antarctica. The main burden of disease is reported in Asia and Africa, but some cases have been reported also in Europe in the past 10 years, especially in returning travellers. Rabies virus has a cylindrical morphology and is a member of the Lyssavirus genus of the Rhabdoviridae family. These viruses are enveloped and have a single stranded RNA genome with negative-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. Rabies lyssavirus has a "negative polarity" (or is a negative-sense RNA virus 3'-5'), which means that its genetic material cannot be directly translated into proteins by the host cell's machinery. Once inside the cytoplasm of a cell, the viral polymerase uses the negative strand as a template to create positive-sense messenger RNA (mRNA) strands. These mRNAs are then translated by the host cell to make proteins, and later to replicate the viral genome. 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.
Structure
Rhabdoviruses have helical symmetry, so their infectious particles are approximately cylindrical in shape. They are characterized by an extremely broad host spectrum ranging from birds to mammals; human-infecting viruses more commonly have icosahedral symmetry and take shapes approximating regular polyhedra. The rabies genome encodes five proteins: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and polymerase (L). All rhabdoviruses have two major structural components: a helical ribonucleoprotein core (RNP) and a surrounding envelope. In the RNP, genomic RNA is tightly encased by the nucleoprotein. Two other viral proteins, the phosphoprotein and the large protein (L-protein or polymerase) are associated with the RNP. The glycoprotein forms approximately 400 trimeric spikes which are tightly arranged on the surface of the virus. The M protein is associated both with the envelope and the RNP and may be the central protein of rhabdovirus assembly. 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 invaginated at the planar end. The core of the virion consists of helically arranged ribonucleoprotein.
Genome organization The rhabdovirus virion is an enveloped, rod- or bullet-shaped structure containing five protein species:
The nucleoprotein (N) coats the RNA at the rate of one monomer of protein to nine nucleotides, forming a nucleocapsid with helical symmetry. Associated with the nucleocapsid are copies of P (phosphoprotein) and L (large) protein. The L protein is well named, its gene taking up about half of the genome. Its large size is justified by the fact that it is a multifunctional protein. The M (matrix) protein forms a layer between the nucleocapsid and the envelope Trimers of G (glycoprotein) form spikes that protrude from the envelope. The genomes of most rhabdoviruses possess the five genes encoding these proteins, as in the case of Rhabdovirus lyssae.
Proteins
Rabies virus is estimated to cause around 55,000 deaths per year across the world and has a death rate of nearly 100%. These statistics coupled with the fact that there is currently no specific treatment, or antiviral drug makes research on the virus of vital importance for the scientific community in order to possibly lower the current death rate. The rabies virus phosphoprotein and polymerase are both important targets for antivirals and are currently used to create the vaccine used for domestic and wild animals. A lot of research is being done to better understand the specific roles and functions of the L-P protein because there is significant evidence already that it could be one of the most important proteins to target for future drugs. There are five proteins that are coded for by the rabies virus genome—phosphoprotein (P), polymerase (L), matrix protein (M), nucleoprotein (N), and glycoprotein (G). These five proteins are transcribed into mRNA in different quantities. The protein transcribed the most is the nucleoprotein, then the phosphoprotein, then the matrix protein, then the glycoprotein and finally the polymerase. Of those proteins, the ones that may be the most important for the functions of the virus are the L-P protein complex. These two proteins are required for the production of all of the proteins utilized by the rabies virus and they interact with many of the other proteins to complete the functions needed by the virus to infect cells, replicate and complete other vital functions. When the structure of the L-P protein was analyzed using UCSF Chimera, it was found that it contained two zinc molecules as well as 2 five-membered rings. The secondary structures were also analyzed, and it was found that there were three different kinds-coil, helix and strand.
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