Rabiesvirus

The rabies virus, also known as rabies virus, a virus attacking the nervous system, which triggers the rabies in animals and humans. The result is an acute life-threatening encephalitis (brain inflammation), which runs usually fatal. The transmission can take place via the saliva of animals.

The rabies virus is an enveloped virus of cylindrical shape. It is a member of the genus Lyssavirus and belongs to the family Rhabdoviridae, whose members have a single-stranded RNA of negative polarity as genome. The genome is completely sequenced. The genetic information is packaged as a ribonucleoprotein complex in which RNA is tightly bound to the viral nucleoprotein N. The RNA genome codes for five genes whose assembly is highly conserved in the genome. It is the gene for nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and the viral RNA polymerase (L).

The transcription and replication found in the cytoplasm of the host cell rather than within specific " virus factories" ( Viroplasmen ), which are the light microscope called a so-called Negri bodies (named after Adelchi Negri ). They have a diameter of 2-10 microns and are typical of rabies infection so that they serve as a pathognomonic feature.

System

The Lyssaviren include commonly associated with rabies rabies virus, various bat lyssavirus and the Mokola virus. Together with the causative agent of Vesikulärstomatitis and further form the Rhabdoviridae family. Rhabdoviridae characteristically have a broad host range, which can range from plants to insects to vertebrates.

Structure

Lyssaviruses have a helical symmetry, the virions have a cylindrical shape. This is in contrast to other viruses that infect humans, which normally have a cubic symmetry.

The rabies virus has an elongated shape with a length of about 180 nm and a diameter of about 75 nm, one end is rounded, while the other is planar. The viral envelope contains so-called "spikes" ( protrusions ), which are formed from the G glycoprotein. These protuberances are missing at the planar end of the virion. Below the cover is a layer of matrix protein M which covers the core of the virion of helical ribonucleoprotein, which is composed of RNA and the N protein.

Genome

The genome consists of unsegmented, linear, single-stranded RNA with negative polarity. The genome is completely sequenced, and has a length of 11,900 nucleotides. The genetic information is packaged as a ribonucleoprotein complex in which RNA is tightly bound to the viral nucleoprotein. The RNA genome codes for five genes, namely the gene for nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein ( G) and the viral RNA polymerase (L). The arrangement 3'- NPMGL -5 ' of these genes is highly conserved.

Replication

Rabies viruses attach to specific receptors on the cell surface and be picked up by a ausbildendes to Endosomvesikel. Inside the endosome, the acidic pH induces the fusion of endosome membrane and the viral envelope. Thus, the capsid reaches the cytosol, decays and releases the genome freely. Both the receptor binding and the membrane fusion, catalyzed by the G glycoprotein that plays an important role in the pathogenesis ( such mutants are not infectious without G).

After penetration into the host cell, the transcription of the viral genome is initiated by the L polymerase to produce more viral proteins. Here P is an essential cofactor for the polymerase L. The viral polymerase recognizes only ribonucleoprotein and free RNA can not use as a template to produce mRNA. Transcription is regulated by cis-elements in the viral genome, as well as by the M protein. The latter is not only essential for the budding ( budding ) of the virus from the membrane, but also regulates the balance between the production and replication of the viral mRNA genome.

Later, the polymerase produces RNA with positive polarity in its entirety. These complementary RNA strands are used as templates to produce new RNA genomes of negative polarity. These are packed with protein N in ribonucleoprotein and can form new viruses.

Transmission

The virus is present in the saliva of a rabid animal and the route of infection almost always leads through a bite. But even the smallest injury to the skin and mucous membranes may allow the virus by contact infection or contact infection penetration. In vitro transmission through mucous membranes has occurred. You may receive an assignment was in this form in people who have researched populated by bats caves. Except in the case of organ transplantation (one case with three deaths in the United States at the beginning of 2004 and a case with three deaths in Germany in early 2005 ), the transmission from human to human has not yet been observed.

From the entry point, the virus travels quickly along the nerve cells in the central nervous system (CNS). The retrograde axonal transport is the most important step in natural rabies infection. The exact molecular basis of this transport are not yet clear, but it has been demonstrated that the phosphoprotein P of rabies virus with the protein DYNLL1 ( LC8 ) interacts the light chain of dynein. P acts also as an interferon antagonist, whereby the immune response is alleviated.

From CNS, the virus spreads to other organs; as it occurs in the saliva of infected animals and can thus further spread. Often occurs an increased aggressiveness with increased biting behavior which the likelihood of spreading the virus further increased.