title: Inhibition of the protease of human immunodeficiency virus blocks replication and infectivity of the virus in chronically infected macrophages.
abstract: Because of the importance of monocytes/macrophages (M/M) as an in vivo reservoir of human immunodeficiency virus (HIV), a study was done to investigate whether viral replication in chronically infected macrophages (HIV M/M) could be inhibited by various drugs, including U-75875, an inhibitor of HIV protease. HIV replication in M/M and in chronically infected T cells was dramatically decreased by U-75875, while other drugs, including zidovudine, interferon-alpha, and an antisense oligodeoxynucleotide against the rev gene, were effective antiviral agents only in de novo-infected cells. Virus titer in HIV M/M was reduced approximately 10(5)-fold by nontoxic concentrations of U-75875, while no effect on HIV DNA or virus antigen expression on cell membrane was achieved in M/M infected either chronically or de novo. Thus, U-75875 essentially worked against late stages of viral replication. These data support the use of protease inhibitors, alone or in combination, in the therapy of HIV-infected patients.
authors.affiliation: Department of Experimental Medicine, University of Rome Tor Vergata, Italy.
authors.forename: C F
authors.initials: CF
authors.lastname: Perno
authors.forename: A
authors.initials: A
authors.lastname: Bergamini
authors.forename: C D
authors.initials: CD
authors.lastname: Pesce
authors.forename: G
authors.initials: G
authors.lastname: Milanese
authors.forename: M
authors.initials: M
authors.lastname: Capozzi
authors.forename: S
authors.initials: S
authors.lastname: Aquaro
authors.forename: S
authors.initials: S
authors.lastname: Thaisrivongs
authors.forename: W G
authors.initials: WG
authors.lastname: Tarpley
authors.forename: G
authors.initials: G
authors.lastname: Zon
authors.forename: C
authors.initials: C
authors.lastname: D'Agostini
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D015757:Genes, rev; D016333:HIV Protease / Q000187:drug effects; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology* / Q000472:pathogenicity; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014774:Virulence; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D017320:HIV Protease Inhibitors; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D009842:Oligopeptides; D013873:Thionucleotides; C065978:U 75875; D015215:Zidovudine; D016333:HIV Protease