HIV-1 virion-associated outer envelope protein gp120 is cleaved at the V3-loop by incubation with recombinant soluble (rs) CD4.

Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.

HIV-1 virion-associated outer envelope protein gp120 is cleaved at the V3-loop by incubation with recombinant soluble (rs) CD4.

Int Conf AIDS. 1992 Jul 19-24;8(1):Mo14 (abstract no. MoA 0051). Unique Identifier : AIDSLINE ICA8/92400007
Werner A; Struble HK; Levy JA; Department of Medicine, University of California, San Francisco.

Abstract: OBJECTIVES: To examine whether proteolytic cleavage of the HIV-1 V3 loop is involved in the virus infection of peripheral blood mononuclear cells (PMC). METHODS: Molecularly cloned and biologically active HIV-1 strains were grown in human PMC. Titration and blocking experiments with rsCD4 were performed in PMC. Virus was purified by filtration, centrifugation through a 28% sucrose cushion, and by sucrose gradient banding. Further purification was done by Sephacryl S-1000 chromatography. Virus suspensions were incubated with rsCD4 at 37 degrees C to determine sensitivity to this molecule. Virus proteins were visualized by immunoblot procedures. RESULTS: HIV-1 virus strains showed various sensitivities to the inhibition of infectivity by rsCD4 TABULAR DATA, SEE ABSTRACT VOLUME. In addition, incubation of purified virus suspensions with rsCD4 led to cleavage of virion-associated gp120 at the V3 loop in a time and rsCD4 concentration-dependent manner. Purified rgp120 served as the negative control, and is not cleaved, even when contaminated with a HIV-2 virus suspension, purified in the same manner as HIV-1. The cleavage can be partially inhibited by PMSF and completely by incubation with a monoclonal antibody directed against the V3 loop. The cleavage time of nonrsCD4 inhibitory virus strains (e.g. HIV-1SF162) are at least two times longer than that for viruses that can be blocked easily. CONCLUSIONS: Exposure of different virus strains to rsCD4 shows varying sensitivity to reduction in infectivity. Concomitantly, this incubation leads to cleavage of virion associated gp120 at the V3 loop in a time and rsCD4 concentration dependent manner, the results suggest that virion associated gp120 is subject to cleavage after attachment with CD4.

Keywords: Antigens, CD4/*METABOLISM Comparative Study Human HIV Envelope Protein gp120/*METABOLISM HIV-1/CLASSIFICATION/*METABOLISM Leukocytes, Mononuclear/MICROBIOLOGY Peptide Fragments/*METABOLISM Recombinant Proteins/METABOLISM Solubility Virion/*METABOLISM ABSTRACT
921230
M92C5340

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