AEGiS-12IAC: Mutations in the leucine zipper-like heptad repeat sequence of HIV-1 gp41 dominantly interferes with wild-type virus infectivity.

12th International AIDS Conference


Geneva, Switzerland - June 28-July 3, 1998

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Mutations in the leucine zipper-like heptad repeat sequence of HIV-1 gp41 dominantly interferes with wild-type virus infectivity.

Int Conf AIDS 1998 Jun 28-Jul 3; 12:6 (abstract no. 11121)

Chen SL, Lee SF, Hao HJ, Lauang LK
Institute of Biomedical Science, Taipei, Taiwan.

OBJECTIVES: We have previously shown that a proline substitution for the conserved leucine or isoleucine residues located in the leucine zipper-like heptad repeat sequence of HIV-1 gp41, whose feature is also conserved among a number of other viruses, renders viruses noninfectious and the envelope (Env) protein unable to mediate membrane fusion. The objective of this study was to utilize the HIV-1 gp41 heptad repeat sequence as a model system to determine the feasibility of developing an antiviral strategy targeting this highly conserved sequence.

METHODS: The interference effect conferred by mutants on infectious virus production was examined by cotransfection of cells with wt and mutant proviruses followed by measurement of the infectivity of the resulting supernatant viruses on SupT1 cells or on a MAGI indicator cell line. The interference conferred by the mutant Env upon the ability of wt protein to mediate virus entry into cells was determined by an env trans-complementation assay using a defective HIV-1 reporter vector.

RESULTS: Viruses obtained from coexpression of wt provirus with mutant 566 or 580 provirus inhibited more potently the production of infectious virus than did viruses produced from mixed transfections showed decreased infectivity compared with that of the wt virus when MAGI assay was performed. The ability of wt Env to induce cytopathic effects was inhibited by coexpression with mutant Env. Coexpression of mutants inhibited the ability of the wt protein to mediate virus-to-cell transmission.

CONCLUSIONS: Our study demonstrates that mutations in the leucine zipper-like heptad repeat sequence dominantly inhibit infectious virus production. These results suggest that the heptad repeat sequence of gp41 can be targeted by trans-dominant negative mutant-based anti-HIV strategies.

Keywords: AEGIS, HIV-1, Leucine Zippers, Mutation, HIV Infections, Proviruses, Membrane Fusion, Cell Line, Transfection, pathogenicity, genetics, ICA12KWDaegis,hiv-1,leucinezippers,mutation,hivinfections,proviruses,membranefusion,cellline,transfection,pathogenicity,genetics,ica12
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