In vitro activation of feline immunodeficiency virus in ramified microglial cells from asymptomatically infected cats

Intravenous infection of cats with feline immunodeficiency virus was used a s a model system to study activation of virus replication in brain-resident microglial cells in vitro. Virus release by ramified microglial cells isol ated from subclinically infected animals was detectable in cell-free tissue culture supernatant only by reverse transcription and nested PCR of gag-sp ecific RNA sequences and not by virion-associated reverse transcriptase act ivity. In contrast, cocultivation of in vivo-infected microglial cells with mitogen-activated peripheral blood mononuclear cells (PBMC) regularly allo ws detection of high virus yields in cell-free tissue culture fluid. Beside s uptake and multiplication of microglia-derived virus in PBMC, release of virus from microglia is stimulated by cell contact with PBMC. The data sugg est that T lymphocytes patrolling the central nervous system could reactiva te the semilatent state of lentiviruses in microglial cells in the course o f clinically silent central nervous system infection.