What is the initial step in HIV entry into the cell regarding envelope protein binding to CD4?

From the Guidelines

The initial step in the entry of HIV into the cell is the binding of gp120 envelope protein to the CD4 protein on the cell surface. This interaction is the first critical step in HIV's infection process, as described in the 2008 recommendations of an international AIDS society-USA panel 1. The gp120 is a glycoprotein located on the surface of the HIV viral envelope that specifically recognizes and attaches to CD4 receptors, which are primarily found on helper T cells, macrophages, and dendritic cells.

• Key points about this process include:
  • The binding of gp120 to CD4 is followed by a conformational change that allows gp120 to interact with chemokine co-receptors (typically CCR5 or CXCR4) on the cell surface, as noted in the study published in Clinical Infectious Diseases 1.
  • This interaction triggers the exposure of gp41, another viral envelope protein, which mediates the fusion of the viral and cellular membranes.
  • Only after these binding and fusion events can the viral contents enter the cell, where the viral RNA-dependent DNA polymerase (reverse transcriptase) will later transcribe the viral RNA genome into DNA.
• The importance of understanding this entry mechanism is highlighted by its role in developing entry inhibitor drugs that target these specific interactions, as discussed in the context of antiretroviral drug resistance testing in adult HIV-1 infection 1.

From the Research

Initial Step in HIV Entry

The initial step in the entry of HIV into the cell involves the binding of a specific envelope protein to the CD4 protein on the cell surface.

• The correct answer is the binding of gp120 envelope protein to the CD4 protein on the cell surface 2, 3, 4, 5.

Role of gp120 and gp41

• gp120 is essential for viral infection as it facilitates HIV entry into the host cell 4.
• gp41 undergoes a series of conformational changes from a non-fusogenic to a fusogenic conformation after gp120 binding to cellular receptors 2.
• The formation of the fusogenic structure brings the viral and cellular membranes close together, a necessary condition for membrane fusion to occur 2.

Interaction with CD4 and Chemokine Receptors

• The gp120 envelope component binds to CD4 on target cells and undergoes conformational changes that allow gp120 to interact with certain G-protein-coupled receptors (GPCRs) on the same target membranes 3.
• The GPCRs that function as HIV coreceptors were found to be chemokine receptors, with CCR5 and CXCR4 being the primary coreceptors 3.