Cystamine potently suppresses in vitro HIV replication in acutely and chronically infected human cells.

Abstract

We have investigated the effects of cystamine on the replication of human 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 MM) that did not show any cytotoxic or cytostatic effects, strongly decreased (> 80%) HIVp24 antigen production and completely abolished the production of infectious viral particles. Cystamine does not affect viral transcription, translation or protein processing; indeed, all HIV proteins are present in a pattern similar to that of nontreated cells. Instead, cystamine interferes with the orderly assembly of HIV virions, as shown by electron microscopy analysis, that reveals only defective viral particles in treated cells. Moreover, suppression of HIV replication, due to the inhibition of proviral DNA formation was observed in acutely infected lymphocytes and macrophages pretreated with cystamine. These results 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 that this compound may represent a new possibility towards the treatment of HIV-1 infection. (J. Clin. Invest. 1994Invest. . 93:2251Invest. -2257

Intravenous Cysteamine Therapy for Nephropathic Cystinosis

“…Examples include apolipoprotein E2 (39) and anti-thrombin III,,ya,a (40). Another possible therapeutic use of cysteamine is in human immunodeficiency virus infections, because cystamine, the disulfide of cysteamine, has recently been shown to inhibit human immunodeficiency virus replication in a cell culture system (41).…”

Human Immunodeficiency Virus Type 1 Infection Modulates the Interleukin (IL)–1β and IL‐6 Responses of Human Macrophages to CD40 Ligand Stimulation

“…These strains were isolated from plasma in PBMC cultures; the supernatants of these cultures were used as the source of the virus. Titration to determine infectivity of Ba-L and primary isolates was done, respectively, in a primary macrophage system or in PBMC as described elsewhere [22,23]. The titers of the virus stocks, expressed as TCID 50 , were determined as described elsewhere [24].…”

Virological and immunological effects of antioxidant treatment in patients with HIV infection

“…ROS have also been shown to enhance HIV replication through activation of NF‐κB [ 11, 12]. Antioxidants such as N‐acetyl cysteine (NAC), glutathione, glutathione‐esters and vitamin C have been demonstrated to inhibit HIV replication in vitro [ 11, 13–21]. Several antioxidants appear to have co‐operative interactions.…”