AEGiS-11IAC: Exposure of non-matured, non-infectious HIV particles to CD4 positive cells.

11th International AIDS Conference


Vancouver, British Columbia — July 7-12, 1996

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Exposure of non-matured, non-infectious HIV particles to CD4 positive cells.

Int Conf AIDS 1996 Jul 7-12; 11:8 (abstract no. We.A.262)
Korn-Muller AC, Nitschko H, Gelderblom H, von der Helm K; Max von Pettenkofer-Institute, University of Munich, Munich, Germany. Fax: 0049-89-5380584.

OBJECTIVE: To investigate the ability of non-matured, non-infectious virus particles to adhere to permissive T lymphocytes and their efficacy to induce syncytia formation, cell death and apoptosis.

METHODS: Non-infectious HIV-1 particles were obtained from cell culture supernatant of chronically infected cells that were treated with different potent HIV-protease (PR) inhibitors. The non-matured character of these virions was confirmed by infectivity assay. The presence of large amounts of non-infectious particles was demonstrated by electron microscopy. To evaluate the ability of these virions not only to adhere to and fuse with target cells, but also to induce syncytia formation and/or cell death, we incubated C8166, Jurkat, H9, MT-4 and PBL target cells with different amounts of non-infectious particles (30-700 non-infectious particles per cell) and analyzed by trypane blue exclusion assay, fluorescence microscopy and fluorescence activated cell scanning (FACScan). During the exposure of target cells to non-infectious virus soluble CD4 or antigp 120 antibody was added prior to "infection" in order to reduce cytopathic effects.

RESULTS: The cytopathic effects of non-matured, non-infectious HIV particles are i) comparable in extent to infectious virus controls, ii) dose-dependent and iii) can be strongly diminished by addition of recombinant soluble CD4 or anti-gp 120 antibody, demonstrating the fusogenic capacity of non-matured virions.

CONCLUSIONS: We suggest that PR-defective particles are likely to play a pathogenic role in the mechanism of lymphocyte depletion, if they do exist in HIV-1 infected individuals. The implications of our data regarding the clinical application of HIV-PR inhibitors could be of major importance for future therapeutical strategies.

Keywords: AEGIS, Antigens, CD4, HIV, HIV-1, Virion, HIV Protease Inhibitors, HIV Envelope Protein gp120, HIV Infections, HIV Protease, HIV Antibodies, Anti-HIV Agents, SK&F 106528, ICA11KWDaegis,antigens,cd4,hiv,hiv-1,virion,hivproteaseinhibitors,hivenvelopeproteingp120,hivinfections,hivprotease,hivantibodies,anti-hivagents,sk&f106528,ica11

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WeA262

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