The prevention of cell adhesion and the cell-to-cell spread of HIV-1 in vitro by the alpha-glucosidase 1 inhibitor, 6-O-butanoyl castanospermine (MDL 28574).
The intercellular adhesion molecule (ICAM-1, CD54) and its counter receptor, the integrin leukocyte function associated antigen 1 (LFA-1, CD11a/CD18), have important roles in the immune response. These include guiding leukocytes to sites of inflammation (Issekutz and Issekutz, 1992), enhancement of antigen presentation (Moy and Brian, 1992) and potentiation of cytotoxic cell function (Umehara et al., 1992; Sanchez-Madrid et al., 1982). In addition to these activities LFA-1 and ICAM-1 are implicated in the cell-to-cell transmission of human immunodeficiency virus (HIV-1) since antibodies to CD18, CD54 or synthetic peptide analogs of ICAM-1 antagonise the formation of virus-induced syncytia (Fecondo et al., 1993; Gruber et al., 1991; Hildreth and Orentas, 1989; Valentin et al., 1990). The alpha-glucosidase 1 inhibitor 6-O-butanoyl castanospermine (MDL 28574) has antiviral activity for HIV which is manifested by a decrease in syncytia as well as the production of virus with altered gp120 and a reduced infectivity (Taylor et al., 1991). Previously, it has been shown that the alpha-glucose 1 inhibitor (MDL 28574) treatment of human leukocytes in vitro or mouse lymphocytes in vivo affects the detection of LFA-1 but not domain 1 of CD4 nor several other CD markers (Bridges et al., submitted for publication). Here, we demonstrate that pre-treatment of HIV-permissive CD4+ cells with MDL 28574 substantially reduces their capacity to bind with cells chronically infected with HIV-1 which results in reduced virus production.(ABSTRACT TRUNCATED AT 250 WORDS)
Marion Merrell Dow Research Institute Laboratory, MRC Collaborative Centre, London, UK.
C G
CG
Bridges
T M
TM
Brennan
D L
DL
Taylor
M
M
McPherson
A S
AS
Tyms
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000821:virology; D002448:Cell Adhesion / Q000187:drug effects*; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D015726:Giant Cells / Q000187:drug effects; D065089:Glycoside Hydrolase Inhibitors; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007212:Indolizines / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D054836:Indolizidines
D065089:Glycoside Hydrolase Inhibitors; D007212:Indolizines; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1; C070715:celgosivir; D054836:Indolizidines