|dc.description.abstract||Rabies is one of the most important diseases. Once clinical signs develop, rabies is almost always fatal. More than 55,000 people die of rabies and millions more receive rabies postexposure prophylaxis each year all over the world. Despite the lethality of rabies, only mild inflammation and little neuronal destruction are observed in the central nervous system (CNS) of rabies patients. On the other hand, laboratory-attenuated rabies virus (RV) induces extensive inflammation and neuronal degeneration in experimentally infected animals. Previous studies have been conducted to investigate what causes the differential effects. It was found that laboratory-attenuated RV induces strong innate immune responses including the expression of inflammatory chemokines and cytokines, IFN and IFN-related genes, as well as Toll-like receptors (TLRs). These observations led to the hypothesis that laboratory-attenuated RV is a potent inducer of host innate immunity, which might be an important mechanism of RV attenuation.
The present study was conducted to further investigate the association between the expression of chemokines and RV infection. Laboratory-attenuated RV (B2C) and wild-type (wt) RV (DRV) were administered to Balb/c mice intramuscularly. Chemokine expression, inflammatory cell infiltration, and blood-brain barrier (BBB) permeability were evaluated at various time points after infection. At 6 day post infection (p.i.), infection with B2C induced the expression of inflammatory chemokines and infiltration of inflammatory cells into the CNS, while these changes were minimal in DRV-infected mice. Furthermore, infection with B2C significantly enhanced BBB permeability compared to infection with DRV. Among the upregulated chemokines, the expression of IP-10 was best correlated with infiltration of inflammatory cells into the CNS and enhancement of BBB permeability.
These data indicate that laboratory-attenuated RV induces chemokines expression and infiltration of inflammatory cells into the CNS. Upregulation of chemokines by B2C may have triggered the change in BBB permeability, which helps infiltration of inflammatory cells into the CNS, and thus attenuation of the effects of RV infection.||