Inhibition of the protease of human immunodeficiency virus blocks replication and infectivity of the virus in chronically infected macrophages.
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.
Perno
C F
CF
Department of Experimental Medicine, University of Rome Tor Vergata, Italy.
Bergamini
A
A
Pesce
C D
CD
Milanese
G
G
Capozzi
M
M
Aquaro
S
S
Thaisrivongs
S
S
Tarpley
W G
WG
Zon
G
G
D'Agostini
C
C
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
D000998:Antiviral Agents; D017320:HIV Protease Inhibitors; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D009842:Oligopeptides; D013873:Thionucleotides; C065978:U 75875; D015215:Zidovudine; D016333:HIV Protease