title: Inhibition of cytokine-driven human immunodeficiency virus type 1 replication by protease inhibitor.
abstract: Protease inhibitors block virus maturation and prevent the spread of human immunodeficiency virus (HIV)-1 in vitro. HIV-1-positive persons produce higher levels of proinflammatory cytokines that up-regulate HIV-1 replication. For the protease inhibitor to be effective in vivo, it must be able to suppress cytokine-induced HIV-1 replication. The in vitro efficacy of protease inhibitor to block tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1alpha, and IL-1beta induction of HIV-1 was investigated. While 100 U/mL of the respective cytokines induced a 208- to 22-fold increase in HIV-1 p24 production, addition of protease inhibitor completely inhibited this virus induction. The kinetics indicated a sustained HIV-1 inhibition despite high levels of endogenous TNF-alpha induction. Dilution of protease inhibitor led to increased HIV-1 replication. These results show that while protease inhibitor can prevent cytokine induction of HIV-1 replication, a continual effective dose is required for the inhibition to be sustained.
authors.affiliation: Department of Immunology/Microbiology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612-3833, USA.
authors.forename: L
authors.initials: L
authors.lastname: Al-Harthi
authors.forename: K A
authors.initials: KA
authors.lastname: Roebuck
authors.forename: H
authors.initials: H
authors.lastname: Kessler
authors.forename: A
authors.initials: A
authors.lastname: Landay
mesh_terms: D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D016207:Cytokines; D017320:HIV Protease Inhibitors; D014409:Tumor Necrosis Factor-alpha