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

Int Conf AIDS 1991 Jun 16-21; 7:25 (abstract no. M.A.14)
Berkower I, Murphy D, Smith GE; CBER FDA, Bethesda, MD, USA

OBJECTIVE: To determine how many recombinant CD4 (rCD4) or CD4-immunoglobulin hybrid molecules must bind each virus to cause inactivation.

METHODS: HIV-1 inactivation by rCD4 and CD4-Ig were measured in a sensitive plaque-forming assay, which gave a quantitative measure of virus survival as a fraction of input virus. The antiviral effects of both agents were blocked by adding excess recombinant gp120, allowing us to compare virus survival as a function of receptor occupancy by rCD4 over the full range of competitor gp120 concentrations.

RESULTS: In the presence of 20nM rCD4, virus survival increased progressively from .03 to .73 as the fraction of viral gp120 receptors occupied by rCD4 decreased from .89 to. 04, due to competitor gp120. For dimeric CD4-Ig, virus survival increased from .02 to .91 as receptor occupancy decreased from .89 to .01. Virus survival followed the Poisson distribution, falling linearly as a semilog function of receptor occupancy by rCD4 and CD4-Ig. At 1/e survival, corresponding to 1 inactivation event per virus, just 1/10th of receptors bound rCD4 and 1/50th bound CD4-Ig.

CONCLUSIONS: These results indicate a functional valency of at least 10 to 50 for viral inactivation by rCD4 and CD4-Ig and support a noncompetitive mechanism of viral inactivation, triggered by rCD4 binding, but not saturating, receptors and suggest that rCD4 may act before or after virus binds to the cell surface.

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