The Preliminary Study Of Cytokine Storm In The Mice Brain During Rabies Virus Infection

Rabies caused by rabies virus infection is a fatal neurological diseases.It can infect almost all mammals including human beings.Rabies virus invades the body mainly through broken skin or mucous membrane.The specific clinical manifestations of rabies are hydrophobia,fear of wind,pharynx muscle cramps,progressive paralysis,etc.In recent years,the number of the deaths caused by rabies among statutory reporting of infectious diseases in China is ranking first,which seriously affect the people's life and health.Cytokine is a kind of small molecular soluble proteins produced and secreted by some immune and non-immune cells,which are stimulated by immunogen?mitogen and other factors.It plays bioactivity at a low concentration.Cytokines binding to its specific receptor stimulate cellular activation,differentiation and protiferation to regulate the body's immune response,facilitate hemopoiesis function.Cytokine storm,also named as hyper cytokinemia,is induced by virus,bacteria and nano-materials.Cytokine excessive expression forms a cytokine storm.When the body is injuried or infected with virus,it produce cytokine to induce inflammatory response,which could activate innate immune response and adaptive immune response to control infection.The level of cytokine would keep a dynamic balance after clearing the infection.However,some virus could break the balance of the level of cytokines,which would make the overexpression of cytokines and form a cytokine storm.The cytokine storm could injury organ even cause death.Researchers have been observed cytokine storm phenomenon in a variety of diseases.The host immune system is activated after infected with rabies virus and producing a series of immune response.Previous study confirmed the rabies virus could induce mouse brain to produce high level interferon alpha/beta(IFN-?/?).In this study,to investigate whether the rabies virus produce cytokine storm in mouse brain or not,the fixed rabies virus strain rRC-HL and Guangxi representative street GX074 were used to construct the chimeric recombinant rabies virus mutants rRC-HLAG?rRC-HLAG242-288?Mu11?rRC-HL?GR333Q and used to innoculate 4-weeks kunming mice brain at 4 and 7 days post-innoculation(dpi),the brain tissue and serum was collected to detect cytokines by ELISA and qPCR,including TNF-??IFN-??IL-1?,IL-6,IL-12 and MCP-1.The results show that rabies virus strains cause to produce high levels of cytokines in mouse brain and the levels of cytokines are related to the virulence.Both virulent and avirulent rabies virus could produce high levels of IL-6 in serum,but only virulent rabies virus could produce high levels of MCP-1 in serum at late infection.These experiments proved that the rabies virus could cause brain to form a cytokine storm on the brink of death,it offers a new way to study pathogenesis rabies.