Age- and host-dependent control of Borna disease virus spread in the developing brains of gerbils and rats

Borna disease virus (BDV) is a non-cytolytic, neurotropic RNA virus that has a broad host range in warm-blooded animals, probably including humans. Recently, we have demonstrated that the neonatal gerbil is a unique model for analyzing BDV-induced acute neurological disease. In this report, to understand the effects of the brain development of gerbils in BDV-induced neuropathogenesis, as well as to investigate the host-dependent differences in BDV propagation and pathogenesis in the brains, we performed experimental infection of BDV using two different infant rodent models, gerbils and rats. We demonstrated here that most of the gerbils infected with BDV on postnatal days (PD) 14, but not on PD1 and PD7, could survive neurological disorders during the observation period of PD85. Interestingly, the levels of BDV RNA and antigen in surviving PD14 inoculated gerbil brains were extremely low, whereas diseased gerbils and both PD7 and PD14 inoculated rats contained significant amounts of BDV antigen in the central nervous system, suggesting that PD14 gerbils successfully controlled BDV spread in the brain. Furthermore, the viral distribution, as well as the expression levels of cytokine and CD8 mRNAs, in the brains was markedly different between the rodent models and between diseased and non-diseased statuses of the gerbils. These results demonstrated that developmentally regulated and host-specific factors could contribute to the prevention of BDV spread in developing animal brains. Studies using different animal systems would provide novel insights into the mechanisms of host defense responses to neurotropic virus infections.