CYSTAMINE POTENTLY SUPPRESSES IN-VITRO HIV REPLICATION IN ACUTELY ANDCHRONICALLY INFECTED HUMAN-CELLS

We have investigated the effects of cystamine on the replication of hu man immunodeficiency virus (HIV) in human lymphocytes and macrophages, the natural targets of HIV in vivo. Treatment of chronically infected macrophages with cystamine, at a concentration (500 mu M) that did no t show any cytotoxic or cytostatic effects, strongly decreased (> 80%) HIV-p24 antigen production and completely abolished the production of infectious viral particles. Cystamine does not affect viral transcrip tion, translation or protein processing; indeed, all HIV proteins are present in a pattern similar to that of nontreated cells. Instead, cys tamine interferes with the orderly assembly of HIV virions, as shown b y electron microscopy analysis, that reveals only defective viral part icles in treated cells. Moreover, suppression of HIV replication, due to the inhibition of proviral DNA formation was observed in acutely in fected lymphocytes and macrophages pretreated with cystamine. These re sults show that cystamine potently suppresses HIV replication in human cells by contemporaneously blocking at least two independent steps of the viral life cycle, without affecting cell viability, suggesting th at this compound may represent a new possibility towards the treatment of HIV-1 infection.