Increased expression of alpha 4 beta 1 and alpha 5 beta 1 integrins on HTLV-I-infected lymphocytes.
T cells interact with the extracellular matrix via integrin receptors and these interactions affect both cellular localization and proliferation. The importance of these interactions in retrovirus-induced diseases, however, remains less clear. In the present study, we investigated changes in T cell adhesion to extracellular matrix proteins by HTLV-I expressing cell lines and human peripheral blood lymphocytes infected with HTLV-I by cocultivation. Cell lines and acutely infected primary peripheral blood lymphocytes demonstrated enhanced adhesion to fibronectin. Acute infection of peripheral blood lymphocytes increased the expression of alpha 5 beta 1 and alpha 4 beta 1 integrins. Antibodies to the alpha 4, alpha 5, and beta 1 subunits inhibited attachment of infected cells to fibronectin. We conclude that HTLV-I infection is associated with an increase in the expression of both the classical fibronectin receptor and the receptor for the alternatively spliced domain of fibronectin on peripheral blood lymphocytes. HTLV-I-related alterations in cell surface adhesion molecules may contribute to the abnormal proliferation of T cells in adult T cell leukemia (ATL) or to the abnormal localization of activated or infected T cells to the central nervous system of patients with tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM).
Dhawan
S
S
Laboratory of Molecular Virology, Food and Drug Administration, Rockville, Maryland 20852.
Weeks
B S
BS
Abbasi
F
F
Gralnick
H R
HR
Notkins
A L
AL
Klotman
M E
ME
Yamada
K M
KM
Klotman
P E
PE
D002448:Cell Adhesion; D002461:Cell Line, Transformed; D005353:Fibronectins; D015368:Human T-lymphotropic virus 1 / Q000254:growth & development*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000096:biosynthesis*; D007797:Laminin; D008214:Lymphocytes / Q000382:microbiology*; D015493:Paraparesis, Tropical Spastic / Q000209:etiology; D017469:Receptors, Fibronectin; D016029:Receptors, Very Late Antigen / Q000096:biosynthesis*; D015682:Retroviridae Proteins, Oncogenic / Q000096:biosynthesis
D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D007797:Laminin; D017469:Receptors, Fibronectin; D016029:Receptors, Very Late Antigen; D015682:Retroviridae Proteins, Oncogenic; C060954:p24 protein, Human T-lymphotropic virus 1