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 rec eptor, the integrin leukocyte function associated antigen 1 (LFA-1, CD 11a/CD18), have important roles in the immune response. These include guiding leukocytes to sites of inflammation (Issekutz and Issekutz, 19 92), enhancement of antigen presentation (Moy and Brian, 1992) and pot entiation of cytotoxic cell function (Umehara et al., 1992; Sanchez-Ma drid et al., 1982). In addition to these activities LFA-1 and ICAM-1 a re implicated in the cell-to-cell transmission of human immunodeficien cy virus (HIV-1) since antibodies to CD18, CD54 or synthetic peptide a nalogs of ICAM-1 antagonise the formation of virus-induced syncytia (F econdo 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 m anifested by a decrease in syncytia as well as the production of virus with altered gp120 and a reduced infectivity (Taylor et al., 1991). P reviously, it has been shown that the alpha-glucose 1 inhibitor (MDL 2 8574) treatment of human leukocytes in vitro or mouse lymphocytes in v ivo affects the detection of LFA-1 but not domain 1 of CD4 nor several other CD markers (Bridges et al., submitted for publication). Here, w e demonstrate that pre-treatment of HIV-permissive CD4(+) cells with M DL 28574 substantially reduces their capacity to bind with cells chron ically infected with HIV-1 which results in reduced virus production. Indirectly, this suggests that compounds of this type, which alter bot h virus ligands and host cell adhesion molecules, may be of especial b enefit in the treatment of viral infections.