Human T-cell leukaemia/lymphoma virus type 1 syncytium formation is regulated in a cell-specific manner by ICAM-1, ICAM-3 and VCAM-1 and can be inhibited by antibodies to integrin beta2 or beta7.
Human T-cell leukaemia/lymphoma virus type 1 (HTLV-1) is a pathogenic retrovirus responsible for a number of inflammatory pathologies and adult T-cell leukaemia. Although T-cell tropic in vivo, HTLV-1 can infect a wide variety of cell types in vitro. Cell-to-cell spread of HTLV-1 may require specific binding of envelope to its cellular receptor, with other cell-surface molecules facilitating fusion. Here it is shown that intercellular adhesion molecule-1 or -3 (ICAM-1, ICAM-3) or vascular cell adhesion molecule-1 (VCAM-1) are required for syncytium formation of K562 with HTLV-1-infected MT2 cells but not C91-PL cells. The effect of ICAMs and VCAM-1 on MT2-induced fusion can be blocked by antibodies that bind beta-integrins. These fusion co-factor molecules are effective only when present in combination with HTLV-1 receptor-bearing cells and are not sufficient to mediate syncytium formation alone. The results suggest that engagement of HTLV-1-infected cells with susceptible target cells requires the simultaneous binding of viral envelope glycoprotein to the cellular receptor and co-factor molecules to beta-integrins. The tissue-specific expression of adhesion molecules might therefore influence HTLV-1 virus tropism and pathogenic changes associated with syncytium formation.
Daenke
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McCracken
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SA
Booth
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D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D005434:Flow Cytometry; D015726:Giant Cells / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D039641:Integrin beta Chains; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D051379:Mice; D014162:Transfection; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
D000914:Antibodies, Viral; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; C483616:ICAM3 protein, human; D039641:Integrin beta Chains; D016023:Integrins; D019010:Vascular Cell Adhesion Molecule-1; C091368:integrin beta7; D018799:Intercellular Adhesion Molecule-1