HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) INFECTION INCREASES THE SENSITIVITY OF MACROPHAGES AND THP-1 CELLS TO CYTOTOXICITY BY CATIONIC LIPOSOMES

Cationic liposomes may be valuable for the delivery of anti-sense olig onucleotides, ribozymes, and therapeutic genes into human immunodefici ency virus type 1 (HIV-1)-infected and uninfected cells, We evaluated the toxicity of three cationic liposomal preparations, Lipofectamine, Lipofectin, and 1,2-dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammoni um bromide (DMRIE) reagent, to HIV-infected and uninfected cells. Mono cyte/macrophages were infected with HIV-1(BaL) and treated with liposo mes in medium containing 20% fetal bovine serum (FBS) for 4 h or 24 h at 37 degrees C. Uninfected monocytic THP-1 cells and chronically infe cted THP-1/HIV-1(IIIB) cells were treated with phorbol 12-myristate 13 -acetate(PMA) and exposed to liposomes in the presence of 10% FBS. Tox icity was evaluated by the Alamar Blue assay and viral p24 production. The toxic effect of cationic liposomes was very limited with uninfect ed cells, although concentrations of liposomes that were not toxic wit hin a few days of treatment could cause toxicity at later times. In HI V-1(BaL)-infected macrophages, Lipofectamine (up to 8 mu M) and Lipofe ctin (up to 40 mu M) were not toxic after a 4-h treatment, while DMRIE reagent at 40 mu M was toxic. While a 4-h treatment of THP-1/HIV-1(II IB) cells with the cationic liposomes was not toxic, even up to 14 day s post-treatment, all three cationic liposomes were toxic to cells at the highest concentration tested after a 24-h treatment. Similar resul ts were obtained with the Alamar Blue assay, Trypan Blue exclusion and a method that enumerates nuclei, Infected cells with relatively high overall viability could be impaired in their ability to produce virion s, indicating that virus production appears to be more sensitive to tr eatment with the cationic liposomes than cell viability. Our results i ndicate that HIV-infected cells are more susceptible than uninfected c ells to killing by cationic liposomes. The molecular basis of this dif ferential effect is unknown; it is proposed that alterations in cellul ar membranes during virus budding cause enhanced interactions between cationic liposomes and cellular membranes.