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Cancer Cell death Cell cycle Cytoskeleton Exo/endocytosis Differentiation Division Organelles Signalling Stem cells Trafficking
Cell Biology International (1998) 22, 95–103 (Printed in Great Britain)
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
NIRIT MOR‑VAKNINa, HAVA TURGEMANa, AMRAM TORGEMANa, MARINA WOLFSONa, MAHMOUD HULEIHELb and MORDECHAI ABOUDa,f1
aDepartment of Microbiology and Immunology, Faculty of Health Sciences; Ben Gurion University of the Negev, Beer Sheva, 84105, Israel
bInstitute of Bioscience Research, Ben Gurion University of the Negev, Beer Sheva, 84105, Israel


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 cytopatic 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.


Key words: HTLV-I, syncytium, TSP/HAM, astrocytes, CNS, blood–brain barrier.

f1*To whom correspondence should be addressed: Prof. Mordechai Aboud; Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel; Email: aboud@bgumail.bgu.ac.il


Received 17 July 1997; accepted 13 January 1998

doi:10.1006/cbir.1998.0241


ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)