Progression of early steps of human immunodeficiency virus type 1 replication in the presence of an inhibitor of viral protease.
We have evaluated a possible role for human immunodeficiency virus type 1 protease during early steps of replication. For these studies, a specific inhibitor of human immunodeficiency virus protease, Ro31-8959, was used. Synthesis of viral cDNA, its integration into cellular DNA, and its transcription were determined during a one-step, acute infection of MT-4 cells. No consistent difference in any of these parameters was noted between control-infected cultures and those treated with protease inhibitor. However, no infectious progeny virus was produced in treated cultures, and thus spread of infection was severely restricted. Our results do not support an essential activity of viral protease in early steps of replication but are in line with its established role in gag and gag-pol processing and in maturation to infectious progeny virus.
Jacobsen
H
H
Department PRTB, F. Hoffmann-LaRoche, Basel, Switzerland.
Ahlborn-Laake
L
L
Gugel
R
R
Mous
J
J
D000998:Antiviral Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D002460:Cell Line; D004279:DNA, Viral / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D016333:HIV Protease / Q000378:metabolism / Q000494:pharmacology; D017320:HIV Protease Inhibitors; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D012367:RNA, Viral / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D019258:Saquinavir; D014158:Transcription, Genetic / Q000187:drug effects; D016662:Virus Integration / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology*
D000998:Antiviral Agents; D004279:DNA, Viral; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D016333:HIV Protease; D019258:Saquinavir