RAPID SYNCYTIUM FORMATION BETWEEN HUMAN T-CELL LEUKAEMIA VIRUS TYPE-I (HTLV-I)-INFECTED T-CELLS AND HUMAN NERVOUS SYSTEM CELLS: A POSSIBLE IMPLICATION FOR TROPICAL SPASTIC PARAPARESIS/HTLV-I ASSOCIATED MYELOPATHY
✍ Scribed by NIRIT MOR-VAKNIN; HAVA TURGEMAN; AMRAM TORGEMAN; MARINA WOLFSON; MAHMOUD HULEIHEL; MORDECHAI ABOUD
- Publisher
- Elsevier Science
- Year
- 1998
- Tongue
- English
- Weight
- 302 KB
- Volume
- 22
- Category
- Article
- ISSN
- 1065-6995
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✦ Synopsis
Tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM), is characterized by infiltration of human T cell leukaemia virus type-I (HTLV-I)-infected T-cells, anti-HTLV-I cytotoxic T cells and macrophages into the patients' cerebrospinal fluid and by intrathecally formed anti-HTLV-I antibodies. This implies that the disease involves a breakdown of the blood-brain barrier. Since astrocytes play a central role in establishing this barrier, the authors investigated the hypothesis that the HTLV-I infected T cells disrupt this barrier by damaging the astrocytes. The present study revealed the HTLV-I-producing T cells conferred a severe cytopathic effect upon monolayers of astrocytoma cell line in co-cultures. Following co-cultivation, HTLV-I DNA and proteins appeared in the monolayer cells, but after reaching a peak their level gradually declined. This appearance of the viral components was proved to result from a fusion of the astrocytic cells with the virus-producing T cells, whereas their subsequent decline reflected the destruction of the resulting syncytia. This fusion could be specifically blocked by anti HTLV-I Env antibodies, indicating that it was mediated by the viral Env proteins expressed on the surface of the virus-producing cells. Similar fusion was observed between the HTLV-I-producing cells and certain other human nervous system cell lines. If such fusion of HTLV-I-infected T cells occurs also with astrocytes and other nervous system cells in TSP/HAM patients, it may account, at least partially, for the blood-brain barrier breakdown and some of the neural lesions in this syndrome.