Gp120 shed from productively-infected cells binds to bystander CD4 + T cells.
Gp120-coated bystander cells are highly sensitivity to ADCC responses mediated by CD4-induced antibodies.
Small-molecule CD4-mimetics redirect CD4-induced antibodies to HIV-1-infected cells.
The hallmark of human immunodeficiency virus type 1 (HIV-1) infection is the progressive depletion of CD4 + T cells. Using cultures of HIV-1-infected cells, we observed that a part of the machinery that the virus uses to infect cells (gp120) binds to uninfected cells. Antibodies elicited during the course of the infection against the gp120 can recognize uninfected cells and redirect an immune response to them that results in their elimination. Importantly, this phenomenon can be blocked with a small CD4-mimetic compound that abrogates the binding of gp120 to uninfected cells and redirects the immune system to infected cells.