What must HIV surface protein do to enter a host cell?

To enter a host cell, the HIV surface protein, specifically the envelope glycoprotein complex (Env), must undergo a series of critical steps:

1. Attachment: The Env complex consists of two subunits: glycoprotein 120 (gp120) and glycoprotein 41 (gp41). The initial step of viral entry involves the attachment of gp120 to specific receptors on the surface of the host cell. These receptors vary depending on the HIV strain but primarily include the CD4 receptor and a co-receptor, either CCR5 or CXCR4.

2. Conformational Change: Upon binding to the CD4 receptor and the co-receptor, gp120 undergoes a significant conformational change, exposing a hydrophobic fusion peptide located within gp41.

3. Fusion: The exposed fusion peptide inserts itself into the host cell membrane, forming a fusion pore. This pore allows the viral envelope to merge with the host cell membrane, creating a direct connection between the viral interior and the cytoplasm of the host cell.

4. Viral Entry: The fusion process leads to the release of the viral core, containing the genetic material (RNA genome) of HIV, into the host cell's cytoplasm.

Throughout these steps, the Env protein plays a crucial role in recognizing and interacting with specific host cell receptors and mediating the fusion of the viral and host cell membranes. Therefore, targeting the Env protein is a key aspect of HIV vaccine development and therapeutic strategies aimed at preventing or blocking viral entry.