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We have analyzed the binding of soluble CD4 (sCD4) to human immunodeficiency virus type 1 (HIV-1) virions (isolates IIIB and RF) at 4 and 37 degrees C by using a combination of gel exclusion chromatography and enzyme-linked immunosorbent assay detection systems. The sCD4 binding curve at 37 degrees C indicates that the affinity of the interaction of sCD4 with gp120 on the virion surface is indistinguishable from the affinity of sCD4 for the equivalent concentration of soluble gp120. At 4 degrees C, however, the affinity of sCD4 for virion-bound gp120 but not for soluble gp120 is reduced by about 20-fold. Binding of sCD4 (greater than 0.2 microgram/ml) to virions at 37 degrees C but not 4 degrees C induces the rapid dissociation of a major proportion of gp120 from gp41 on the virion surface. This dissociation requires occupancy by sCD4 of multiple (probably two) binding sites on a gp120-gp41 oligomer. At 37 degrees C there are two components to the neutralizing action of sCD4 on HIV-1; reversible, competitive inhibition at low sCD4 concentrations (less than 0.2 microgram/ml) and essentially irreversible inhibition due to gp120 loss at higher sCD4 concentrations. At 4 degrees C, sCD4 neutralizes HIV infectivity by competitive inhibition alone. These findings may have implications for the HIV-CD4+ cell binding and fusion reactions and the mechanism by which sCD4 blocks infectivity.

Original publication

DOI

10.1128/jvi.65.3.1133-1140.1991

Type

Journal article

Journal

Journal of virology

Publication Date

03/1991

Volume

65

Pages

1133 - 1140

Addresses

Chester Beatty Laboratories, Institute of Cancer Research, London, United Kingdom.

Keywords

Cell Line, Humans, HIV-1, Virion, Recombinant Proteins, HIV Envelope Protein gp120, Enzyme-Linked Immunosorbent Assay, Neutralization Tests, Protein Binding, Kinetics, CD4 Antigens