title: 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.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, 84105, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Mor-Vaknin
authors.forename: H
authors.initials: H
authors.lastname: Turgeman
authors.forename: A
authors.initials: A
authors.lastname: Torgeman
authors.forename: M
authors.initials: M
authors.lastname: Wolfson
authors.forename: M
authors.initials: M
authors.lastname: Huleihel
authors.forename: M
authors.initials: M
authors.lastname: Aboud
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001253:Astrocytes / Q000473:pathology*; D001254:Astrocytoma / Q000473:pathology; D001812:Blood-Brain Barrier; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology* / Q000821:virology; D016923:Cell Death; D002459:Cell Fusion / Q000187:drug effects; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003588:Cytopathogenic Effect, Viral; D004279:DNA, Viral / Q000032:analysis / Q000096:biosynthesis; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D015726:Giant Cells; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D007668:Kidney; D051379:Mice; D009442:Neurilemmoma / Q000473:pathology; D009447:Neuroblastoma / Q000473:pathology; D015493:Paraparesis, Tropical Spastic / Q000473:pathology* / Q000821:virology; D051381:Rats; D015682:Retroviridae Proteins, Oncogenic / Q000032:analysis / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014617:Vacuoles; D054301:gag Gene Products, Human Immunodeficiency Virus
chemical_list: D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D004279:DNA, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D015682:Retroviridae Proteins, Oncogenic; D054301:gag Gene Products, Human Immunodeficiency Virus; C060955:p19 protein, Human T-lymphotropic virus 1