Peripheral Nerve Injury Induced by Japanese Encephalitis Virus in C57BL/6 Mouse

Japanese encephalitis virus (JEV), with neurotoxic and neuroinvasive properties, is the major cause of human viral encephalitis in Asia. Although Guillain-Barre syndrome caused by JEV infections is not frequent, a few cases have been reported in recent years. To date, no existing animal model for JEV-induced peripheral nerve injury (PNI) has been established, and thus the pathogenic mechanism is not clarified. Therefore, an animal model is urgently required to clarify the correlation between JEV infection and PNI. In the present study, we used JEV GIb strain of NX1889 to establish a mouse model of JEV infection. The general neurological signs emerged on day 3 of modeling. The motor function continued to deteriorate, reaching a maximum at 8 to 13 days postinfection (dpi) and gradually recovered after 16 dpi. The injuries of 10(5) PFU and 10(6) PFU groups were the most severe. Transmission electron microscopy and immunofluorescence staining showed varying degrees of demyelination and axonal degeneration in the sciatic nerves. The electrophysiological recordings demonstrated the presence of demyelinating peripheral neuropathy with reduced nerve conduction velocity. The decreased amplitudes and the prolonged end latency revealed axonal-type motor neuropathy. Demyelination is predominant in the early stage, followed by axonal injury. The expression level of JEV-E protein and viral RNA was elevated in the injured sciatic nerves, suggesting that it may cause PNI at the early stage. Inflammatory cell infiltration and increased inflammatory cytokines indicated that neuroinflammation is involved in JEV-induced PNI.

Automated summary

This study established a mouse model of JEV infection using JEV GIb NX1889 strain. The model showed general neurological signs on day 3, with motor function deteriorating the most in the 10^5 PFU and 10^6 PFU groups. Microscopy and immunofluorescence staining revealed varying degrees of demyelination and axonal degeneration in the sciatic nerves. Electrophysiological recordings demonstrated peripheral neuropathy with reduced nerve conduction velocity. Increased expression of JEV-E protein and viral RNA in the injured sciatic nerves suggested its role in early stage PNI. Inflammatory cell infiltration and increased inflammatory cytokines indicated neuroinflammation involvement in JEV-induced PNI.