The role of antibody Fc-mediated effector functions in controlling or preventing infections
by human immunodeficiency type 1 (HIV-1) and simian immunodeficiency (SIV) viruses has been recently highlighted in
multiple studies. One of those effector functions, antibody-dependent cellular cytotoxicity (ADCC) was suggested as
correlating with decreased HIV-1 acquisition risk in the recent Thai RV144 vaccine trial. RV144-elicited antibodies with
potent ADCC activity were recently found to recognize HIV envelope (Env) epitopes exposed upon Env-CD4 interaction.
However, HIV-1 efficiently limits the exposure of those epitopes by strongly downregulating CD4 by both Nef and Vpu
accessory proteins, as well as indirectly preventing the accumulation of Env at the cell surface by Vpu-mediated BST-2
antagonism. These accessory proteins were thus proposed to play a critical role in decreasing the susceptibility of HIVinfected
cells to elimination by ADCC. In this review we will summarize these recent findings and discuss the critical role
that HIV-1 envelope glycoproteins conformation plays on ADCC responses, how these responses can be measured in the
laboratory, the role of HIV-1-transmission on ADCC responses and how this knowledge can be used to develop new
strategies aimed at targeting HIV-1-infected cells.
Keywords: ADCC, BST-2, CD4, envelope glycoproteins, HIV-1, gp120, gp41, non-neutralizing antibodies, Nef, Vpu.
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