AEGiS-11IAC: Capillary endothelial cells derived from human brain tumors are permissive for HIV-infection.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Capillary endothelial cells derived from human brain tumors are permissive for HIV-infection.

Int Conf AIDS 1996 Jul 7-12; 11:217 (abstract no. Tu.A.143)
Oltrogge J, von Briesen H, Engelhardt B, Pereda-Fernandez C, Woelki U, Schlote W, Lorenz R, Rubsamen-Waigmann H, Unger RE; Chemotherapeutical Research Institute, Georg-Speyer-Haus, Frankfurt, Germany. Fax: 0049 69 633 95 297.

OBJECTIVE: Infection with the human immunodeficiency virus (HIV) not only results in immune system dysfunction (AIDS) but also frequently in a dementing neurological disorder of the brain, or AIDS dementia complex (ADC), which can be clinically distinguished from other CNS complications due to AIDS. Individuals with ADC exhibit abnormalities in motor, cognitive and behavioral functions, which become progressively worse as the health status declines. Virus has been detected within macrophage, glial and neuronal cells in the brain, and ADC is believed to be a consequence of infection of these cells. How HIV crosses the blood-brain barrier made up of tightly packed brain capillary endothelial cells, which is normally impermeable to other cells, bacteria, viruses or antibodies, to reach these target cells within the brain is not known. The objective was to isolate human brain capillary endothelial cells (HBCE) and to determine their infectivity with different HIV-subtypes and the consequences of HIV-infection.

METHODS: Optimal conditions were established for the recovery, isolation and maintenance of human brain capillary endothelial cells (HBCE) from freshly removed brain tumors such as meningiomas, glioblastomas, adenocarcinomas in tissue culture systems from HIV-seronegative adults. A number of different freshly isolated HIV-subtypes as well as lab strains of HIV which exhibited different in vitro cell tropisms were used for infectivity studies and the effects on cytopathology of HBCE, replication of virus, and interaction with other cells were examined.

RESULTS: Endothelial cells were isolated from cells that grew out of brain capillary segments recovered by enzymatic digestions and gradient centrifugations of homogenized brain tumors. Cultures were greater than 95% endothelial cells after the second passage and could be maintained for at least 10 passages. These cells formed similar tight junctions as seen in vivo, which are responsible for the impermeability of the blood-brain barrier and exhibited typical endothelial von Willebrand-factor staining and binding of UEA-1. Preliminary HIV-infectivity experiments indicated that infection of HBCE occurred but was dependent on viral subtype and the method of propagation of viral stocks.

CONCLUSIONS: Different HIV-subtypes appear to differ in their ability to infect and replicate in HBCE. The examination of HBCE and their interaction with other primary cells and various HIV-subtypes will provide explanations of how these interactions may allow virus to cross or affect the blood-brain barrier and potentiate the onset of ADC in vivo.

Keywords: AEGIS, HIV Infections, Capillaries, HIV, AIDS Dementia Complex, Blood-Brain Barrier, Acquired Immunodeficiency Syndrome, Brain Neoplasms, Virus Replication, HIV Envelope Protein gp120, Brain, Macrophages, HIV Core Protein p24, HIV Envelope Protein gp160, Tropism, Brain Diseases, Central Nervous System, Adult, Human, In Vitro, virology, ICA11

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