A mouse model of peripheral nerve injury induced by Japanese encephalitis virus

Abstract

Japanese encephalitis virus (JEV) is the most important cause of acute encephalitis in Eastern/Southern Asia. Infection with this virus also induces peripheral nerve injury. However, the disease pathogenesis is still not completely understood. Reliable animal models are needed to investigate the molecular pathogenesis of this condition. We studied the effect of Japanese encephalitis virus infection in C57BL/6 mice after a subcutaneous challenge. Limb paralysis was determined in mice using behavioral tests, including a viral paralysis scale and the hanging wire test, as well as by changes in body weight. Nerve conduction velocity and electromyography testing indicated the presence of demyelinating neuropathy of the sciatic nerve. Pathological changes in neural tissues were examined by immunofluorescence and transmission electron microscopy, which confirmed that the predominant pathologic change was demyelination. Although Western blots confirmed the presence of the virus in neural tissue, additional studies demonstrated that an immune-induced inflammatory response resulted in severe never injury. Immunofluorescence confirmed the presence of Japanese encephalitis virus in the brains of infected mice, and an inflammatory reaction was observed with hematoxylin-eosin staining as well. However, these observations were inconsistent at the time of paralysis onset. In summary, our results demonstrated that Japanese encephalitis virus infection could cause inflammatory demyelination of the peripheral nervous system in C57BL/6 mice.