title: L-cycloserine, an inhibitor of sphingolipid biosynthesis, inhibits HIV-1 cytopathic effects, replication, and infectivity.
abstract: Drugs that reduce viral production or prevent viral spread by interference with the host's cellular components are unlikely to induce resistance, in contrast to treatment modalities that interact with the HIV-1 life cycle. Two features make L-cycloserine (L-CS) a candidate drug of this kind: (a) L-CS is a potent inhibitor of the sphingolipid pathway (b) sphingolipids, galactocerebrosides, and sulfatides have been shown, by others, to bind gp120. In a feasibility and efficacy study, we have found that L-CS inhibits HIV-1 replication in a CD4+ lymphoid cell line (CEM) as documented by the reduction of syncytium formation, the number of HIV-1 infected cells, and p24 protein production. This observation may lead to a new strategy for the treatment of HIV-1 infection.
authors.affiliation: Department of Pediatrics, Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Mizrachi
authors.forename: M
authors.initials: M
authors.lastname: Lev
authors.forename: Z
authors.initials: Z
authors.lastname: Harish
authors.forename: S K
authors.initials: SK
authors.lastname: Sundaram
authors.forename: A
authors.initials: A
authors.lastname: Rubinstein
mesh_terms: D000963:Antimetabolites / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology / Q000821:virology; D002460:Cell Line; D003523:Cycloserine / Q000494:pharmacology*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D015726:Giant Cells; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D013107:Sphingolipids / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology
chemical_list: D000963:Antimetabolites; D016655:HIV Core Protein p24; D013107:Sphingolipids; D003523:Cycloserine