Effect of soluble CD4 on exposure of epitopes on primary, intact, native human immunodeficiency virus type I virions of different genetic clades

We have used a virus-binding assay to examine conformational changes that o ccur when soluble CD4 (sCD4) binds to the surface of intact, native, primar y human immunodeficiency virus type 1 virions. The isolates examined belong to seven genetic clades (A to H) and are representative of syncytium-induc ing and non-syncytium-inducing phenotypes. Conformational changes in epitop es in the C2, V2, V3, C5, and CD4 binding domain (CD4bd) of gp120 and the c luster I and II regions of gp41 of these viruses were examined using human monoclonal antibodies that are directed at these regions. The studies revea led that sCD4 binding causes a marked increase in exposure of epitopes in t he V3 loop, irrespective of the clade or the phenotype of the virus. Sporad ic increases in exposure were observed in some epitopes in the V2 region, w hile no changes were observed in the C2, C5, or CD4bd of gp120 or the clust er I and II regions of gp41.