The main cell population affected by the human immunodeficiency virus-1 (HIV-1) infection belongs to the CD4+ T-lymphocyte family. Recent convincing evidence indicates that the majority of the cells that die due to HIV-1 are not actually infected by the virus. Instead, these cells are being led to programmed cell death after the activation of apoptotic mechanisms by the virus or its components. We propose here from accumulated evidence that the virus appears to deregulate the physiological function of these cells during the process of antigen presentation. Ionic interactions between the variable V3 domain of the HIV-1 coat glycoprotein gp120 and the amino terminal of the chemokine receptor CCR5 play a prominent role in this process, and we speculate that nature has evolved simple electrostatic interaction mechanisms which, coupled to specific recognition systems on the cell surface, can initiate and modulate certain cellular events without the need for specific molecular structures. HIV-1 utilizes such a mechanism to ensure activation of the target host cell.