HTLV-I production based on activation of integrin/ligand signaling in HTLV-I-infected T cell lines derived from HAM/TSP patients.
OBJECTIVE
Activity of integrin/ligand signaling leading to activation of small GTPases might regulate the efficiency of cell-to-cell spread of human T lymphotropic virus type I (HTLV-I) through the virological synapse. We compared both activity of small GTPases and involvement of integrin/ligand signaling in extracellular release of HTLV-I virions between each three HTLV-I-infected T cell lines derived from HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients and from other origins as a control.


METHODS
Activity of small GTPases (Rho, Rac and Cdc42) was analyzed by pull-down assay with suppressive effect of both HTLV-I production and HTLV-I tax mRNA expression by anti-integrin-blocking antibodies.


RESULTS
All small GTPases were strongly activated in all cell lines derived from HAM/TSP patients, but not in control cell lines except one cell line. Treatment of all cell lines derived from HAM/TSP patients, but not all control cell lines, with anti-integrin-blocking antibodies significantly suppressed the level of HTLV-I p19 antigen in culture supernatants without downregulation of HTLV-I tax mRNA expression.


CONCLUSIONS
Significant involvement with integrin/ligand signaling in extracellular release of HTLV-I virions in cell lines derived from HAM/TSP patients suggests that HTLV-I-infected cells in HAM/TSP patients have the potential for the efficient spread of HTLV-I to uninfected cells.
Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Naomi
N
Fukushima
Tatsufumi
T
Nakamura
Yoshihiro
Y
Nishiura
Hiroaki
H
Ida
Toshiyuki
T
Aramaki
Katsumi
K
Eguchi
D002460:Cell Line; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008024:Ligands; D015493:Paraparesis, Tropical Spastic / Q000276:immunology / Q000821:virology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D014771:Virion / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D016356:Gene Products, tax; D016023:Integrins; D008024:Ligands; C514970:tax protein, Human T-lymphotrophic virus 1; D020558:GTP Phosphohydrolases; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins