HIV-1 proteinase is required for synthesis of pro-viral DNA.
HIV-1 proteinase activity is thought to occur primarily post-integration by cleaving the viral Gag and Gag-Pol polyproteins. Its role in the pre-integration stages of viral replication, however, has not been studied in detail. Here we report that a synthetic peptide analogue, UK-88,947, which is a specific inhibitor of purified HIV-1 proteinase, inhibits the processing of the viral polyproteins in cultures of HIV-1 infected cells and prevents the formation of mature, infectious virions. Analysis of DNA from HIV-1 infected cells treated with UK-88,947 showed that viral DNA synthesis was inhibited when the compound was added to cultures one hour before infection. Similar results were obtained when AZT was used. Neither HIV-1 reverse transcriptase or the replication of FIV are inhibited by UK-88,947.
Baboonian
C
C
Clinical Research Centre, Harrow, Middlesex, England.
Dalgleish
A
A
Bountiff
L
L
Gross
J
J
Oroszlan
S
S
Rickett
G
G
Smith-Burchnell
C
C
Troke
P
P
Merson
J
J
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics*; D016333:HIV Protease / Q000378:metabolism* / Q000494:pharmacology; D017320:HIV Protease Inhibitors; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000187:drug effects / Q000502:physiology; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D009842:Oligopeptides / Q000494:pharmacology*; D011533:Proviruses / Q000235:genetics* / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D015345:Oligonucleotide Probes; D009842:Oligopeptides; D011994:Recombinant Proteins; C070642:UK 88947; D015215:Zidovudine; D016333:HIV Protease