Re-evaluation of the involvement of the adhesion molecules ICAM-1/LFA-1 in syncytia formation of HIV-1-infected subclones of a CEM T-cell leukemic line.
The role of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and LFA-1 in human immunodeficiency virus type 1 (HIV-1)-induced cell fusion was investigated in subclones of a T-cell leukemic cell line (CEM) with differing abilities to form syncytia. Addition of monoclonal antibodies 84H10 directed against ICAM-1 and MHM23 directed against the common beta subunit of LFA-1 (CD18) resulted in greater than 50% suppression of syncytia formation in cultures of these clones infected with cell-free virus. Two subclones, 2G5-144-84 and 2G5-1, were deficient in their ability to form syncytia and expressed reduced amounts of LFA-1 compared with the parental line. The expression of ICAM-1 but not LFA-1 was upregulated on the clones following treatment with interferon-gamma (IFN gamma); however, this did not overcome the delay in syncytia formation observed in these cells. The syncytia-positive subclones 1B11-39 and 17D-9 expressed high levels of LFA-1. Basal expression of ICAM-1 was upregulated on these cells by treatment with tumor necrosis factor-alpha (TNF alpha), which also accelerated and enhanced syncytia formation. However, anti-ICAM-1 and anti-LFA-1 (CD18) antibodies did not reverse the TNF alpha-induced enhancement of syncytia formation of HIV-1-infected clones 1B11-39 and 17D-9. Under conditions of low viral expression, adhesion molecules may contribute to syncytia formation if adequate levels of both receptor and ligand in the ICAM-1/LFA-1 complex are expressed.(ABSTRACT TRUNCATED AT 250 WORDS)
Gruber
M F
MF
Division of Cytokine Biology and Virology, Food and Drug Administration, National Institutes of Health, Bethesda, MD 20892.
Webb
D S
DS
Gerrard
T L
TL
Mostowski
H S
HS
Vujcic
L
L
Golding
H
H
D000911:Antibodies, Monoclonal / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D002459:Cell Fusion; D002999:Clone Cells; D015726:Giant Cells / Q000382:microbiology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D012194:RNA-Directed DNA Polymerase