The Preliminary Study Of Effect On Tau Protein Phosphorylation In The Mice Brain During Rabies Virus Infection

Rabies is a zoonotic and fatal neurological disease caused by rabies virus. Its main clinical features are acute encephalomyelitis. According to the world health organization reported, more than 70,000 people died of rabies each year worldwide. Dogs remain the most important reservoir for human rabies in Asia and Africa, where most human rabies cases occur. Yet the incidence rate of China arranged the second, after India's largest number cases in the world.Tau proteins belong to the family of microtubule-associated proteins (MAPs). They are mainly expressed in the axons of the central and peripheral nervous system where they play an important role in the assembly of tubulin monomers into microtubules to stabilize the neuronal microtubules network. Tau is a kind of phosphoprotein, and regulates the stability of microtubules through phosphorylation. The hyperphosphorylation of Tau protein abnormal aggregation itself form the neurofibrillary tangles (NFTs) with neurotoxicity. The phosphorylated Tau protein loses the function of prompting the microtubules gathered, which leads to the microtubule depolymerization, axonal transport barriers and neuron dysfunction. That caused neural degenerative diseases. Meanwhile, the microtubules play a crucial role on the virus and virus protein retrograde and anterograde transport process.In order to explore whether the rabies virus infection in mice after influence on the phosphorylation of Tau protein in the brain, then we make use of the rabies virus fixed poison rRC-HL and CVS-24, the street strong toxic strains GX01, GX074 and GXN119, as well as the recombinant virus strains rRC-HL?G, rRC-HL?G242-288 and rRC-HL?G253/263/273 which were rescued by our laboratory, to inject the 4-week-old kunming mice brain. And we took the brain tissue process Western-blot experiments. Results indicated that, rabies attenuate virus rRC-HL cannot cause the Tau protein phosphorylation after intracerebrally injection, while the strong virus can cause phosphorylated Tau protein in the brain. In addition, when the mice appeared the depressed, numbness, paralysis and severe clinical symptoms, we could detecte the Tau phosphorylation. At the same time we also found that, the level of the Ser396 site phosphorylation is higher than Ser202 site. The chimeric recombinant rabies virus G protein pathogenic function and Tau protein phosphorylation was significantly positive correlation. In the mouse brain, the corresponding Tau protein molecular weight was increased after the Tau phosphorylated, and might form the Tau protein oligomers, and abnormal phosphorylated Tau protein self assembled form tangles, lead to neuronal dysfunction, the specific mechanisms of change need further research.