The Routes Of Japanese Encephalitis Virus Entry Into The Central Nervous System

Japanese encephalitis(JE)is a zoonosis caused by Japanese encephalitis virus(JEV)infection.JEV is a mosquito-borne and typically neurotropic virus.JEV crosses the blood-brain barrier and enters the central nervous system(CNS),which is the key step leading to encephalopathy.The mechanism by which the virus gains entry to the brain(neuroinvasion)remains poorly understood,although the routes that other members of the flavivirus family enter central nervous system have been reported.JEV is a serious threat for human health;however there is still lack of no specific antiviral drugs for the disease.Therefore,exploring the pathogenesis of the encephalitis,especially the routes of JEV entering the central nervous system,is significant for the prevention and treatment of the disease.In this study,we investigated the rountes of JEV gaining entry to the brain.The C57BL/6 mouse were infected with JEV.After infection,the brain,olfactory bulb and spinal cord of the mouse were taken as sample every day,then RT-PCR and immunofluorescence were conducted to detect viruses in those tissues.The results showed that the time of the virus entering the brain is always earlier than the olfactory bulb and the spinal cord.To find out the cell types that carries virus to CNS,Then,CD3+T cells,CD19+B cells or Ly6c+monocytes incubated with JEV were intracranially injected to the healthy mouse brains.The viruses in the brain were detected once mouse showing clinical sign.The expression of chemokine receptors on monocytes and T cells was determined by flow cytometry.In vitro coculture also showed that monocytes were prone to adhere to the endothelial cells after incubated with JEV.Finally,adhesion molecules and their ligands on monocytes and endothelial cells increased after the virus infection.In a summary,JEV gains entry to the central nervous system by hematogenous routs.The JEV can infect various immune cells,such as CD3+T cells,CD19+B cells or Ly6c+monocytes.The JEV infection promotes the monocytes adhesion with endothelial cells of blood-brain barrier,leading to a high probability of these cells cross blood-brain barrier and entry into central nervous system.