Abstract
OBJECTIVE: Anti-human immunodeficiency virus (HIV) immunotoxins are potential treatments for HIV infection. but they may also be used as probes to study the relationship between HIV and the cell it infects. Data from the present study indicate the complexity of this relationship.DESIGN: A panel of monoclonal antibodies directed against different epitopes on the HIV envelope protein(s) gp l20 and gp 41 was conjugated to ricin A chain. The activity of these immunotoxins on HIV-infected cell lines was studied.RESULTS: The data demonstrate that HIV-infected cell lines may be killed by some, but not all, of these immunotoxins. The killing is not directly proportional to the binding of the antibody to the infected cell and is influenced by the viral strain. The immunotoxins were used to select persistently infected cell lines for immunotoxin-resistant variants: these demonstrate several different viral or cellular defects. The incubation of infected cells with a soluble form of the viral receptor increases the sensitivity of the cells to anti-gp41, but not anti-gpl20, immunotoxins by altering both the levels of expression and internalization of the viral envelope. Drugs that inhibit lysosomal degradation (ammonium chloride, monensin. chloroquine) enhance the efficacy of these immunotoxins.CONCLUSIONS: Because immunotoxins must be internalized to function, they may be used to study the intracellular trafficking of the target antigens. In the present study, this was done using the HIV-envelope protein as expressed in infected cells as the target antigen