Interactions between brain endothelial cells and human T-cell leukemia virus type 1-infected lymphocytes: Mechanisms of viral entry into the central nervous system

Human T-cell leukemia virus type 1 (HTLV-1) is associated with a variety of clinical manifestations. including tropical spastic paraparesis or HTLV-1- associated myelopathy (TSP/HAM). Viral detection in the central nervous sys tem (CNS) of TSP/HAM patients demonstrates the ability of HTLV-1 to cross t he blood-brain barrier (BBB). To investigate viral entry into the CNS, rat brain capillary endothelial cells were exposed to human lymphocytes chronic ally infected by HTLV-1 (MT2), to lymphocytes isolated from a seropositive patient, or to a control lymphoblastoid cell line (CEM). An enhanced adhesi on to and migration through brain endothelial cells in vitro was observed w ith HTLV-1-infected lymphocytes. HTLV-1-infected lymphocytes also induced a twofold increase in the paracellular permeability of the endothelial monol ayer. These effects were associated with an increased production of tumor n ecrosis factor alpha by HTLV-1-infected lymphocytes in the presence of brai n endothelial cells. Ultrastructural analysis showed that contact between e ndothelial cells and HTLV-1-infected lymphocytes resulted in a massive and rapid budding of virions from lymphocytes, followed by their internalizatio n into vesicles by brain endothelial cells and apparent release onto the ba solateral side, suggesting that viral particles may cross the BBB using the transcytotic pathway. Our study also demonstrates that cell-cell fusion oc curs between HTLV-1-infected lymphocytes and brain endothelial cells, with the latter being susceptible to transient HTLV-1 infection. These aspects m ay help us to understand the pathogenic mechanisms associated with neurolog ical diseases induced;by HTLV-1 infection.