The relevance of HIV env/CD4 interactions to the pathogenesis of acquired immune deficiency syndrome

Abstract

The survey of the characteristics of HIV infection implicates the binding of HIV env to the CD4 receptor as the principal cause of the resulting immunodeficiency. There is evidence that such binding selectively impairs self-recognition. The resulting immunodeficiency syndrome has the characteristics of graft vs. host disease, consistent with chronic allogeneic and semiallogeneic GVHD in mouse-models. since these syndromes are believed to result from triggering the established immunoregulatory mechanisms necessary to maintain self-tolerance, vaccination to prevent AIDS should aim to correct the inability of the HIV host mount an immune response against CD4 binding epitopes on HIV gp120, preferably without exposing the vaccine to intact envelope glycoprotein. Since the AIDS syndrome is probably a defect in net-work immunoregulation, the most appropriate target for therapy and for vaccination is the idiotype of anti-CD4 antibodies that block CD4/env interaction.