7th International AIDS Conference Florence, Italy — June 16-21, 1991

Int Conf AIDS 1991 Jun 16-21; 7:26 (abstract no. M.A.17)
Butini L, Pantaleo G, Poli G, Dayton A, Fauci AS; LIR, NIAID, NIH, Bethesda, MD, USA

OBJECTIVE: To determine the role of the LFA-1/ICAM-1/2 pathway of cell adhesion in the process of HIV-mediated cell fusion and HIV spreading.

METHODS: Jurkat cells were transfected with HXB2, a plasmid that contains a full length, infectious human T lymphotropic virus (HTLV)-IIIB. PHA-activated LFA-1+ and LFA-1(-) [obtained from a leukocyte adhesion deficiency (LAD) patient] peripheral blood mononuclear cells (PBMC) were inoculated with supernatants (SN) containing either HIV-1LAV or HIV-2ROD. Anti-LFA-1 (anti-CD18), anti-ICAM-1 and anti-ICAM-2 mAb and rCD4 were added to the cultures of Jurkat cells or PHA-activated LFA-1+ PBMC immediately after transfection or inoculation respectively, and read every two days. Cell cultures were observed daily for syncytia formation and monitored for viral production by assay of culture SN for reverse transcriptase (RT) activity.

RESULTS: High concentrations (10 mug/ml) of anti-LFA-1 mAb significantly inhibited HIV replication in both experimental conditions as measured by RT activity. Inhibition of the peak RT activity was 50 +/- 3% (mean +/- standard deviation) as obtained from 4 independent experiments on HIV-1 infected LFA-1+ PBMC, whereas it was 45 +/- 5% (mean +/- standard deviation) from 3 independent experiments on Jurkat cells transfected with HXB2. Lower concentrations of anti-LFA-1 had no significant antiviral activity in both experimental conditions. Similar results were obtained on PHA-activated LFA-1+ PBMC inoculated with HIV-2. In contrast, syncytia formation was completely suppressed, even at the lowest concentration of anti-LFA-1 used (1 mug/ml). Anti-ICAM-1 and anti-ICAM-2 mAb used alone or in combination did not suppress either virus replication or syncytia formation; furthermore, anti-LFA-1 mAb but not anti-ICAM-1/2 mAb cooperated with rCD4 in suppressing HIV infection in both experimental conditions. In LFA-1(-) PBMC inoculated either with HIV-1 or HIV-2 efficient viral spreading occurred whereas syncytia formation was never observed.

CONCLUSIONS: These results indicate that: a) LFA-1 is required for HIV-mediated cell fusion; b) the partial inhibitory effect of anti-LFA-1 mAb cannot be explained by inhibition of cell-to-cell spreading of HIV; c) the lack of antiviral activity of ICAM-1/2 mAb suggests the existence of an additional ligand for LFA-1 other than ICAM-1/2.

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