The risk for rabies transmission varies in part with the species of biting animal, the anatomic site of the bite, and the severity of the wound. Specific symptoms develop as either encephalitis or paralysis. Initial symptoms of rabies include fever, headache, malaise, and upper respiratory and gastrointestinal tract disorders, which can last 4-10 days. NOT A RABIES VIRUS A herpesvirus that predominantly infects swine, but can also infect a range of other mammals, including rodents Rabies virus in which the envelope gene has been replaced with the envelope gene from another virus Rabies virus that has been mutated from the original wild-type sequence PLEASE NOTE: The following are Stanford Biosafety definitions for the following terms, and may not be the consistent elsewhere. This pseudotyping alters the cell tropism of the virus and can be useful for specific experimental purposes. Pseudotyped rabies virus: Rabies virus in which the rabies envelope gene is deleted can be pseudotypes with a number of different envelope genes, including EnvA, VSV-g, avian sarcoma leucosis virus glycoprotein, or HIV env.
Therefore, there is essentially no risk to generate replication competent rabies virus. In general, as the rabies virus is a negative-strand RNA virus, it does not integrate into the cell genome and has no chance to produce a G protein RNA template. Thus the resultant virus becomes a “mono-synaptic” transneuronal tracer and significantly reduces the biohazardous risk because the virus has no potential to infect or trans-synaptically transport to any mammalian cells, including human and mice. In short, the risk for infection is specified by transgene expression and retrograde transport is limited to a single synapse. If the virus is able to infect a TVA-positive neuron, it can replicate and strongly label the first-order (initially infected) neurons, but since its genome lacks the B19 glycoprotein, it cannot infect other neurons by itself. Since mammalian neurons do not express TVA, the injected virus cannot infect wild-type human neurons. Second modification: This alters the tropism of the virus so that it cannot infect any mammalian cells except those that express a genetically-specified neuronal population transgene which encodes the envelope receptor (TVA) of this pseudotyped virus. If the B19-glycoprotein is (intentionally) over-expressed as a transgene in a defined group of infected cells, the virus can trans-synaptically transport to adjacent cells only (single-step) and never go beyond. As a result, the mutant virus cannot spread to any other surrounding cells from the originally infected cells. Initial deletion: This modification deletes a gene which encodes the rabies virus envelope B19- glycoprotein (RG) and which is required for the production of competent or infectious viral particles from the virus genome in transduced cells. The benefit is the ability to trace a neural circuit on the cellular level as only connected/attached neurons are affected. mCherry makes the infected cells glow red so they are visible under a microscope.
This modified version of the rabies virus forces neurons it infects to produce a red fluorescent protein called mCherry. SADdG-mCherry/EnvASADdG is an example of a modified rabies virus. Recombinant rabies virus vectors: Replication-deficient rabies vectors can be useful tools for investigation into neuronal trafficking or targeted expression in neurons. Family Rhabdoviridae, genus Lyssavirus bullet-shaped, enveloped virus approximately 75nm in diameter by 180 nm in length single-stranded, negative-sense RNA genome.
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