6th International AIDS Conference


San Francisco, California, USA — June 20-23, 1990

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Influence of acylation inhibitors on the infectivity of HIV-1 in vitro.

Int Conf AIDS 1990 Jun 20-23; 6:339 (abstract no. 1103)
Saermark T, Kleinschmidt A, Erfle V; The Protein Laboratory, University of Copenhagen, DK-2200 Copenhagen, DK

OBJECTIVE: Influence of acylation inhibitors (like cerulenin and myristic acid analogues) on the release of infectious virus particles.

METHODS: Infected cells were incubated with the acylation inhibitors in various concentrations for 24-48 hours. Virus release was demonstrated by incubation of the supernatant with HIV-1 susceptible LC5, followed by immunoperoxidase staining for viral antigens five days after reinfection. Control experiments for the effect of glucosamine were carried out with glucose.

RESULTS: Tetradecanal and myristoylated glycine were both found to be competitive inhibitors of N-Myristoyl Transferase (NMT) and of myristoylation of p17gag and p27nef. Glucosamine also inhibited NMT activity and acylation. We showed that these acylation inhibitors reduced the release of infective viral particles from LC5 cells. In contrast to cerulenin these are non-toxic and do not affect protein synthesis in the concentration used. Glucosamine also inhibited virus release.

CONCLUSION: Inhibition of myristoylation in HIV-1 infected cells results in a reduced release of HIV-1 presumably due to inhibited acylation of p17 gag. The inhibitors are non-toxic to cells.

Keywords: AEGIS, Acylation, HIV-1, Myristic Acid, Virion, HIV Protease Inhibitors, Cerulenin, In Vitro, pathogenicity, ICA6KWDaegis,acylation,hiv-1,myristicacid,virion,hivproteaseinhibitors,cerulenin,invitro,pathogenicity,ica6

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