Figure 1.

A generic illustration of the initial attachment of HIV-1 to a CD4⁺ cell, resulting in in a series of sequential steps that allows viral replication. Initial HIV-1 cell contact result in the interaction of viral envelope glycoprotein gp120 with CD4 receptors, to form a (1) gp120/CD4 complex on the host cell surface (4). This interaction induces a conformational change in the envelope protein that exposes a chemokine receptor binding site. (2 and 3) Association of gp120 with chemokine receptor CC chemokine receptor 5 (CCR5) or chemokine receptor 4 (CXCR4), promotes a rearrangement of the transmembrane envelope protein gp41, resulting in the (4) fusion of the viral and cellular membranes and the entry of the viral capsid into the cell (4–6). CXCR4 and CCR5 were initially identified for their role in HIV-1 entry of CD4⁺ T cells through its interaction with gp120 (7). CCR5 is a G protein-coupled receptor (8), with seven transmembrane segments and an eighth α-helix parallel to the plasma membrane (6). (5) Viral RNA is now released into the cell, followed by (6) reverse transcriptase to HIV-1 DNA; (7) integration and transcription in the nucleus; (8) translation and assembly in the cell cytoplasm; followed by (9) budding and release and maturation. Diagram created with BioRender (https://biorender.com/).