In vivo infection of ramified microglia from adult cat central nervous system by feline immunodeficiency virus

Infection of microglial cells by the human immunodeficiency virus (HIV) is supposed to play an important role in the pathogenesis of AIDS-related cent ral nervous system (CNS) complications. So far, however, experimental data about interactions between HIV and ramified microglia from the adult CNS we re only occasionally reported, making it difficult to understand the exact nature of pathogenic events contributing to HIV-encephalopathy. Therefore, we used the animal model of feline immunodeficiency virus (FIV) infection o f domestic cats to establish an experimental system which Is suitable for s tudying the relationships between an immunodeficiency virus and the mature ramified microglia of the central nervous system. By means of density gradi ent centrifugation approximately 95% pure microglial cells could be isolate d from adult feline brain that were characterized by their CD45(low) phenot ype. Resident microglia extracted from the CNS of experimentally infected c ats harbored FIV-specific DNA and cocultivation with mitogen-activated, but uninfected peripheral blood mononuclear cells (PBMC) resulted in recovery of high-titered infectious virus. Double labeling of brain cell monoculture s explanted from persistently infected animals for both microglia and FIV m arkers disclosed less than 1% of viral antigen expressing microglial cells. This suggests that during the subclinical phase of the infection only a sm all number of brain-resident macrophages are productively infected. However , interaction of FIV-infected microglia and inflammatory lymphocytes may pr omote viral replication, thus supporting viral spread in brain tissue. (C) 2000 Academic Press.