Borna disease virus persistence causes inhibition of glutamate uptake by feline primary cortical astrocytes

Borna disease virus (BDV), a nonsegmented, negative-stranded (NNS) RNA viru s, causes central nervous system (CNS) disease in a broad range of vertebra te species, including felines. Both viral and host factors contribute to ve ry diverse clinical and pathological manifestations associated with BDV inf ection. BDV persistence in the CNS can cause neurobehavioral and neurodevel opmental abnormalities in the absence of encephalitis. These BDV-induced CN S disturbances are associated with altered cytokine and neurotrophin expres sion, as well as cell damage that is very restricted to specific brain regi ons and neuronal subpopulations. BDV also targets astrocytes, resulting in the development of prominent astrocytosis. Astrocytes play essential roles in maintaining CNS homeostasis, and disruption of their normal activities c an contribute to altered brain function. Therefore, we have examined the ef fect of BDV infection on the astrocyte's physiology. We present here eviden ce that BDV can establish a nonlytic chronic infection in primary cortical feline astrocytes that is associated with a severe impairment in the astroc ytes' ability to uptake glutamate. In contrast, the astrocytes' ability to uptake glucose, as well as their protein synthesis, viability, and rate of proliferation, was not affected by BDV infection. These findings suggest th at, in vivo, BDV could also affect an important astrocyte function required to prevent neuronal excitotoxicity. This, in turn, might contribute to the neuropathogenesis of BDV.