Single-Molecule Super-Resolution Imaging of T-Cell Plasma Membrane CD4 Redistribution upon HIV-1 Binding

Area of Science:

• Cell Biology
• Virology
• Immunology

Background:

• Cellular entry of HIV-1 involves envelope protein (Env) binding to CD4 and co-receptors (CCR5/CXCR4) on host cells.
• The nanoscale redistribution of these receptors during virus binding is not well understood.

Purpose of the Study:

• To quantitatively investigate nanoscale changes in CD4 organization on CD4+ T cells upon HIV-1 binding.
• To understand the spatial dynamics of host cell receptors during viral entry.

Main Methods:

• Utilized single-molecule super-resolution imaging to analyze CD4 distribution.
• Quantitatively assessed changes in CD4 cluster size and molecule number before and after HIV-1 binding.

Main Results:

• CD4 molecules were primarily observed as individual units or small clusters (up to 4 molecules).
• HIV-1 binding induced a 3-to-10-fold increase in the diameter and molecule number of CD4 clusters at the site of virus attachment.
• Recombinant gp120 also induced a similar, though less pronounced, CD4 reorganization.

Conclusions:

• This study provides the first quantitative data on nanoscale CD4 reorganization triggered by HIV-1 on CD4+ T cells.
• The findings offer a robust methodology for characterizing plasma membrane receptor organization and its functional implications.