Single-molecule super-resolution imaging of t-cell plasma membrane cd4 redistribution upon hiv-1 binding

Yue Yuan, Caron A. Jacobs, Isabel Llorente Garcia, Pedro M. Pereira, Scott P. Lawrence, Romain F. Laine, Mark Marsh, Ricardo Henriques

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


The first step of cellular entry for the human immunodeficiency virus type-1 (HIV-1) occurs through the binding of its envelope protein (Env) with the plasma membrane receptor CD4 and co-receptor CCR5 or CXCR4 on susceptible cells, primarily CD4+ T cells and macrophages. Although there is considerable knowledge of the molecular interactions between Env and host cell receptors that lead to successful fusion, the precise way in which HIV-1 receptors redistribute to sites of virus binding at the nanoscale remains unknown. Here, we quantitatively examine changes in the nanoscale organisation of CD4 on the surface of CD4+ T cells following HIV-1 binding. Using single-molecule super-resolution imaging, we show that CD4 molecules are distributed mostly as either individual molecules or small clusters of up to 4 molecules. Following virus binding, we observe a local 3-to-10-fold increase in cluster diameter and molecule number for virus-associated CD4 clusters. Moreover, a similar but smaller magnitude reorganisation of CD4 was also observed with recombinant gp120. For one of the first times, our results quantify the nanoscale CD4 reorganisation triggered by HIV-1 on host CD4+ T cells. Our quantitative approach provides a robust methodology for characterising the nanoscale organisation of plasma membrane receptors in general with the potential to link spatial organisation to function.

Original languageEnglish
Article number142
Issue number1
Publication statusPublished - Jan 2021


  • CD4
  • HIV-1 entry
  • Modelling
  • Nanoscale cluster
  • Quantitative analysis
  • Super-resolution microscopy
  • Viral receptor


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