6th International AIDS Conference


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

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Mechanism of HIV-1 assembly - role of GAG myristoylation and ENV synthesis.

Int Conf AIDS 1990 Jun 20-23; 6:322 (abstract no. 1035)
Ratner L, Vander Heyden N, Bryant M; Department of Medicine, Washington University, St. Louis, Missouri, USA

OBJECTIVE: To define the roles of GAG myristoylation and ENV synthesis in HIV-1 particle assembly.

METHODS: Viral stocks were derived from molecular clones with an alteration of the N-terminal myristoyl-acceptor amino acid of GAG, or with in-frame or frame-shift deletions in the first conserved domain of the SU envelope protein.

RESULTS: Substitution of the myristoyl-acceptor glycine with alanine, in a functional clone of HIV-1, eliminates virus replication. Complementation of this defect in trans, restores infectious particle production. The non-myristoylated (myr-) gag precursor accumulates in infected cells and is not processed into the mature capsid components of the intact virion. However, myr-Pr55gag can be processed by purified HIV protease in vitro, demonstrating that the myristoyl moiety is not required for cleavage by the protease. Myristoylation of Pr55gag is not necessary for localization but is required for stable membrane association and assembly of HIV-1. In-frame or frame-shift deletions of env do not affect the ability of transfected proviral clones to give rise to virus particles, but these particles are non-infectious in CEM, MOLT3, and H9 T lymphoid cell lines. These particles have a density of 1.14 on sucrose sedimentation gradients, are trypsin-resistant and triton-sensitive.

CONCLUSIONS: Myristoylation of GAG is important for HIV-1 assembly by stabilizing its interaction with the membrane. ENV is not required for virus particle formation. Further understanding of the mechanisms of virus particle assembly will be important in development of specific antiviral agents targetting this step in replication.

Keywords: AEGIS, HIV-1, Myristic Acid, Virus Replication, Virion, Virus Assembly, HIV-1 Reverse Transcriptase, HIV Protease, Cell Line, In Vitro, virology, ICA6KWDaegis,hiv-1,myristicacid,virusreplication,virion,virusassembly,hiv-1reversetranscriptase,hivprotease,cellline,invitro,virology,ica6

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